Thu . 20 Jul 2020
TR | RU | UK | KK | BE |

Long non-coding RNA

long non-coding rna, long noncoding rna database
Long non-coding RNAs long ncRNAs, lncRNA are defined as transcripts longer than 200 nucleotides that are not translated into protein This somewhat arbitrary limit distinguishes long ncRNAs from small non-coding RNAs such as microRNAs miRNAs, small interfering RNAs siRNAs, Piwi-interacting RNAs piRNAs, small nucleolar RNAs snoRNAs, and other short RNAs LncRNAs are sometimes referred to as long intergenic noncoding RNAs lincRNAs, which specifies that they are found in between coding genes rather than antisense to them or within introns


  • 1 Abundance
  • 2 Genomic organization
  • 3 Translation
  • 4 Conservation
  • 5 Functions
    • 51 In the regulation of gene transcription
      • 511 In gene-specific transcription
      • 512 Regulating basal transcription machinery
      • 513 Transcribed by RNA polymerase III
    • 52 In post-transcriptional regulation
      • 521 In splicing
      • 522 In translation
      • 523 In siRNA-directed gene regulation
    • 53 In epigenetic regulation
      • 531 Imprinting
      • 532 Xist and X-chromosome inactivation
      • 533 Telomeric non-coding RNAs
  • 6 In aging and disease
  • 7 See also
  • 8 References


A recent study found only one-fifth of transcription across the human genome is associated with protein-coding genes, indicating at least four times more long non-coding than coding RNA sequences However, it is large-scale complementary DNA cDNA sequencing projects such as FANTOM Functional Annotation of Mammalian cDNA that reveal the complexity of this transcription The FANTOM3 project identified ~35,000 non-coding transcripts from ~10,000 distinct loci that bear many signatures of mRNAs, including 5’ capping, splicing, and poly-adenylation, but have little or no open reading frame ORF While the abundance of long ncRNAs was unanticipated, this number represents a conservative lower estimate, since it omitted many singleton transcripts and non-polyadenylated transcripts tiling array data shows more than 40% of transcripts are non-polyadenylated However, unambiguously identifying ncRNAs within these cDNA libraries is challenging since it can be difficult to distinguish protein-coding transcripts from non-coding transcripts It has been suggested through multiple studies that testis, and neural tissues express the greatest amount of long non-coding RNAs of any tissue type Using FANTOM5, 27,919 long ncRNAs have been identified in various human sources

Quantitatively, lncRNAs demonstrate ~10-fold lower abundance than mRNAs in a population of cells, which is explained by higher cell-to-cell variation of expression levels of lncRNA genes in the individual cells, when compared to protein-coding genes In general, the majority ~78% of lncRNAs are characterized as tissue-specific, as opposed by only ~19% of mRNAs In addition to higher tissue specificity, lncRNAs are characterized by higher developmental stage specificity, and cell subtype specificity in heterogeneous tissues, such as human neocortex

Big efforts have been put into investigating lncRNAs in plant species, since they remain far more uninvestigated than in mammal species An extensive study considering 37 higher plant species and six algae came out at the end of 2015 and identified ~200,000 non-coding transcripts using an in-silico approach With this study it was created the Green Non-Coding Database GreeNC, which is a repository of plant lncRNAs

Genomic organization

In 2005 the landscape of the mammalian genome was described as numerous 'foci' of transcription that are separated by long stretches of intergenic space While long ncRNAs are located and transcribed within the intergenic stretches, the majority are transcribed as complex, interlaced networks of overlapping sense and antisense transcripts that often include protein-coding genes, giving rise to a complex hierarchy of overlapping isoforms Genomic sequences within these transcriptional foci are often shared within a number of different coding and non-coding transcripts in the sense and antisense directions For example, 3012 out of 8961 cDNAs previously annotated as truncated coding sequences within FANTOM2 were later designated as genuine ncRNA variants of protein-coding cDNAs While the abundance and conservation of these interleaved arrangements suggest they have biological relevance, the complexity of these foci frustrates easy evaluation

The GENCODE consortium has collated and analysed a comprehensive set of human lncRNA annotations and their genomic organisation, modifications, cellular locations and tissue expression profiles Their analysis indicates human lncRNAs show a bias toward two-exon transcripts


There has been considerable debate about whether lncRNAs have been misannotated and do in fact encode proteins Several lncRNAs have been found to in fact encode for peptides with biologically significant function Ribosome profiling studies have suggested that anywhere from 40% to 90% of annotated lncRNAs are in fact translated, although there is disagreement about the correct method for analyzing ribosome profiling data Additionally, it is thought that many of the peptides produced by lncRNAs may be highly unstable and without biological function


Initial studies into lncRNA conservation noted that as a class, they were enriched for conserved sequence elements, depleted in substitution and insertion/deletion rates and depleted in rare frequency variants, indicative of purifying selection maintaining lncRNA function However, further investigations into vertebrate lncRNAs revealed that while lncRNAs are conserved in sequence, they are not conserved in transcription In other words, even when the sequence of a human lncRNA is conserved in another vertebrate species, there is often no transcription of a lncRNA in the orthologous genomic region Some argue that these observations suggest non-functionality of the majority of lncRNAs, while others argue that they may be indicative of rapid species-specific adaptive selection

While the turnover of lncRNA transcription is much higher than initially expected, it is important to note that still, hundreds of lncRNAs are conserved at the sequence level There have been several attempts to delineate the different categories of selection signatures seen amongst lncRNAs including: lncRNAs with strong sequence conservation across the entire length of the gene, lncRNAs in which only a portion of the transcript eg 5' end, splice sites is conserved, and lncRNAs that are transcribed from syntenic regions of the genome but have no recognizable sequence similarity Additionally, there have been attempts to identify conserved secondary structures in lncRNAs, though these studies have currently given way to conflicting results


Large-scale sequencing of cDNA libraries and more recently transcriptomic sequencing by next generation sequencing indicate that long noncoding RNAs number in the order of tens of thousands in mammals However, despite accumulating evidence suggesting that the majority of these are likely to be functional, only a relatively small proportion has been demonstrated to be biologically relevant As of January 2016, 294 LncRNAs have been functionally annotated in LncRNAdb a database of literature described LncRNAs, with the majority of these 183 LncRNAs being described in humans As of June 2017, a total of 959 human lncRNAs that with experimental evidences have been community-curated in LncRNAWiki a wiki-based, publicly editable and open-content platform for community curation of human lncRNAs A further large-scale sequencing study provides evidence that many transcripts thought to be lncRNAs may, in fact, be translated into proteins

In the regulation of gene transcription

In gene-specific transcription

In eukaryotes, RNA transcription is a tightly regulated process NcRNAs can target different aspects of this process, targeting transcriptional activators or repressors, different components of the transcription reaction including RNA polymerase RNAP II and even the DNA duplex to regulate gene transcription and expression In combination these ncRNAs may comprise a regulatory network that, including transcription factors, finely control gene expression in complex eukaryotes

NcRNAs modulate the function of transcription factors by several different mechanisms, including functioning themselves as co-regulators, modifying transcription factor activity, or regulating the association and activity of co-regulators For example, the ncRNA Evf-2 functions as a co-activator for the homeobox transcription factor Dlx2, which plays important roles in forebrain development and neurogenesis Sonic hedgehog induces transcription of Evf-2 from an ultra-conserved element located between the Dlx5 and Dlx6 genes during forebrain development Evf-2 then recruits the Dlx2 transcription factor to the same ultra-conserved element whereby Dlx2 subsequently induces expression of Dlx5 The existence of other similar ultra- or highly conserved elements within the mammalian genome that are both transcribed and fulfil enhancer functions suggest Evf-2 may be illustrative of a generalised mechanism that tightly regulates important developmental genes with complex expression patterns during vertebrate growth Indeed, the transcription and expression of similar non-coding ultraconserved elements was shown to be abnormal in human leukaemia and to contribute to apoptosis in colon cancer cells, suggesting their involvement in tumorigenesis

Local ncRNAs can also recruit transcriptional programmes to regulate adjacent protein-coding gene expression For example, divergent lncRNAs that are transcribed in the opposite direction to nearby protein-coding genes comprise a significant proportion ~20% of total lncRNAs in mammalian genomes possibly regulate the transcription of nearby adjacent essential developmental regulatory genes in pluripotent cells

The RNA binding protein TLS, binds and inhibits the CREB binding protein and p300 histone acetyltransferease activities on a repressed gene target, cyclin D1 The recruitment of TLS to the promoter of cyclin D1 is directed by long ncRNAs expressed at low levels and tethered to 5’ regulatory regions in response to DNA damage signals Moreover, these local ncRNAs act cooperatively as ligands to modulate the activities of TLS In the broad sense, this mechanism allows the cell to harness RNA-binding proteins, which make up one of the largest classes within the mammalian proteome, and integrate their function in transcriptional programs Nascent long ncRNAs have been shown to increase the activity of CREB binding protein, which in turn increases the transcription of that ncRNA A recent study found that a lncRNA in the antisense direction of the Apolipoprotein A1 APOA1 regulates the transcription of APOA1 through epigenetic modifications

Recent evidence has raised the possibility that transcription of genes that escape from X-inactivation might be mediated by expression of long non-coding RNA within the escaping chromosomal domains

Regulating basal transcription machinery

NcRNAs also target general transcription factors required for the RNAP II transcription of all genes These general factors include components of the initiation complex that assemble on promoters or involved in transcription elongation A ncRNA transcribed from an upstream minor promoter of the dihydrofolate reductase DHFR gene forms a stable RNA-DNA triplex within the major promoter of DHFR to prevent the binding of the transcriptional co-factor TFIIB This novel mechanism of regulating gene expression may in fact represent a widespread method of controlling promoter usage given that thousands of such triplexes exist in eukaryotic chromosome The U1 ncRNA can induce transcription initiation by specifically binding to and stimulating TFIIH to phosphorylate the C-terminal domain of RNAP II In contrast the ncRNA 7SK, is able to repress transcription elongation by, in combination with HEXIM1/2, forming an inactive complex that prevents the PTEFb general transcription factor from phosphorylating the C-terminal domain of RNAP II, thereby repressing global elongation under stressful conditions These examples, which bypass specific modes of regulation at individual promoters to mediate changes directly at the level of initiation and elongation transcriptional machinery, provide a means of quickly affecting global changes in gene expression

The ability to quickly mediate global changes is also apparent in the rapid expression of non-coding repetitive sequences The short interspersed nuclear SINE Alu elements in humans and analogous B1 and B2 elements in mice have succeeded in becoming the most abundant mobile elements within the genomes, comprising ~10% of the human and ~6% of the mouse genome, respectively These elements are transcribed as ncRNAs by RNAP III in response to environmental stresses such as heat shock, where they then bind to RNAP II with high affinity and prevent the formation of active pre-initiation complexes This allows for the broad and rapid repression of gene expression in response to stress

A dissection of the functional sequences within Alu RNA transcripts has drafted a modular structure analogous to the organization of domains in protein transcription factors The Alu RNA contains two ‘arms’, each of which may bind one RNAP II molecule, as well as two regulatory domains that are responsible for RNAP II transcriptional repression in vitro These two loosely structured domains may even be concatenated to other ncRNAs such as B1 elements to impart their repressive role The abundance and distribution of Alu elements and similar repetitive elements throughout the mammalian genome may be partly due to these functional domains being co-opted into other long ncRNAs during evolution, with the presence of functional repeat sequence domains being a common characteristic of several known long ncRNAs including Kcnq1ot1, Xlsirt and Xist

In addition to heat shock, the expression of SINE elements including Alu, B1, and B2 RNAs increases during cellular stress such as viral infection in some cancer cells where they may similarly regulate global changes to gene expression The ability of Alu and B2 RNA to bind directly to RNAP II provides a broad mechanism to repress transcription Nevertheless, there are specific exceptions to this global response where Alu or B2 RNAs are not found at activated promoters of genes undergoing induction, such as the heat shock genes This additional hierarchy of regulation that exempts individual genes from the generalised repression also involves a long ncRNA, heat shock RNA-1 HSR-1 It was argued that HSR-1 is present in mammalian cells in an inactive state, but upon stress is activated to induce the expression of heat shock genes The authors found that this activation involves a conformational alteration to the structure of HSR-1 in response to rising temperatures, thereby permitting its interaction with the transcriptional activator HSF-1 that subsequently undergoes trimerisation and induces the expression of heat shock genes In the broad sense, these examples illustrate a regulatory circuit nested within ncRNAs whereby Alu or B2 RNAs repress general gene expression, while other ncRNAs activate the expression of specific genes

Transcribed by RNA polymerase III

Many of the ncRNAs that interact with general transcription factors or RNAP II itself including 7SK, Alu and B1 and B2 RNAs are transcribed by RNAP III, thereby uncoupling the expression of these ncRNAs from the RNAP II transcriptional reaction they regulate RNAP III also transcribes a number of additional novel ncRNAs, such as BC2, BC200 and some microRNAs and snoRNAs, in addition to the highly expressed infrastructural ‘housekeeping’ ncRNA genes such as tRNAs, 5S rRNAs and snRNAs The existence of an RNAP III-dependent ncRNA transcriptome that regulates its RNAP II-dependent counterpart was supported by a recent study that described a novel set of ncRNAs transcribed by RNAP III with sequence homology to protein-coding genes This prompted the authors to posit a ‘cogene/gene’ functional regulatory network, showing that one of these ncRNAs, 21A, regulates the expression of its antisense partner gene, CENP-F in trans

In post-transcriptional regulation

In addition to regulating transcription, ncRNAs also control various aspects of post-transcriptional mRNA processing Similar to small regulatory RNAs such as microRNAs and snoRNAs, these functions often involve complementary base pairing with the target mRNA The formation of RNA duplexes between complementary ncRNA and mRNA may mask key elements within the mRNA required to bind trans-acting factors, potentially affecting any step in post-transcriptional gene expression including pre-mRNA processing and splicing, transport, translation, and degradation

In splicing

The splicing of mRNA can induce its translation and functionally diversify the repertoire of proteins it encodes The Zeb2 mRNA, which has a particularly long 5’UTR, requires the retention of a 5’UTR intron that contains an internal ribosome entry site for efficient translation However, retention of the intron is dependent on the expression of an antisense transcript that complements the intronic 5’ splice site Therefore, the ectopic expression of the antisense transcript represses splicing and induces translation of the Zeb2 mRNA during mesenchymal development Likewise, the expression of an overlapping antisense Rev-ErbAa2 transcript controls the alternative splicing of the thyroid hormone receptor ErbAa2 mRNA to form two antagonistic isoforms

In translation

NcRNA may also apply additional regulatory pressures during translation, a property particularly exploited in neurons where the dendritic or axonal translation of mRNA in response to synaptic activity contributes to changes in synaptic plasticity and the remodelling of neuronal networks The RNAP III transcribed BC1 and BC200 ncRNAs, that previously derived from tRNAs, are expressed in the mouse and human central nervous system, respectively BC1 expression is induced in response to synaptic activity and synaptogenesis and is specifically targeted to dendrites in neurons Sequence complementarity between BC1 and regions of various neuron-specific mRNAs also suggest a role for BC1 in targeted translational repression Indeed, it was recently shown that BC1 is associated with translational repression in dendrites to control the efficiency of dopamine D2 receptor-mediated transmission in the striatum and BC1 RNA-deleted mice exhibit behavioural changes with reduced exploration and increased anxiety

In siRNA-directed gene regulation

In addition to masking key elements within single-stranded RNA, the formation of double-stranded RNA duplexes can also provide a substrate for the generation of endogenous siRNAs endo-siRNAs in Drosophila and mouse oocytes The annealing of complementary sequences, such as antisense or repetitive regions between transcripts, forms an RNA duplex that may be processed by Dicer-2 into endo-siRNAs Also, long ncRNAs that form extended intramolecular hairpins may be processed into siRNAs, compellingly illustrated by the esi-1 and esi-2 transcripts Endo-siRNAs generated from these transcripts seem particularly useful in suppressing the spread of mobile transposon elements within the genome in the germline However, the generation of endo-siRNAs from antisense transcripts or pseudogenes may also silence the expression of their functional counterparts via RISC effector complexes, acting as an important node that integrates various modes of long and short RNA regulation, as exemplified by the Xist and Tsix see above

In epigenetic regulation

Epigenetic modifications, including histone and DNA methylation, histone acetylation and sumoylation, affect many aspects of chromosomal biology, primarily including regulation of large numbers of genes by remodeling broad chromatin domains While it has been known for some time that RNA is an integral component of chromatin, it is only recently that we are beginning to appreciate the means by which RNA is involved in pathways of chromatin modification

In Drosophila, long ncRNAs induce the expression of the homeotic gene, Ubx, by recruiting and directing the chromatin modifying functions of the trithorax protein Ash1 to Hox regulatory elements Similar models have been proposed in mammals, where strong epigenetic mechanisms are thought to underlie the embryonic expression profiles of the Hox genes that persist throughout human development Indeed, the human Hox genes are associated with hundreds of ncRNAs that are sequentially expressed along both the spatial and temporal axes of human development and define chromatin domains of differential histone methylation and RNA polymerase accessibility One ncRNA, termed HOTAIR, that originates from the HOXC locus represses transcription across 40 kb of the HOXD locus by altering chromatin trimethylation state HOTAIR is thought to achieve this by directing the action of Polycomb chromatin remodeling complexes in trans to govern the cells' epigenetic state and subsequent gene expression Components of the Polycomb complex, including Suz12, EZH2 and EED, contain RNA binding domains that may potentially bind HOTAIR and probably other similar ncRNAs This example nicely illustrates a broader theme whereby ncRNAs recruit the function of a generic suite of chromatin modifying proteins to specific genomic loci, underscoring the complexity of recently published genomic maps Indeed, the prevalence of long ncRNAs associated with protein coding genes may contribute to localised patterns of chromatin modifications that regulate gene expression during development For example, the majority of protein-coding genes have antisense partners, including many tumour suppressor genes that are frequently silenced by epigenetic mechanisms in cancer A recent study observed an inverse expression profile of the p15 gene and an antisense ncRNA in leukaemia A detailed analysis showed the p15 antisense ncRNA CDKN2BAS was able to induce changes to heterochromatin and DNA methylation status of p15 by an unknown mechanism, thereby regulating p15 expression Therefore, misexpression of the associated antisense ncRNAs may subsequently silence the tumour suppressor gene contributing towards cancer


Many emergent themes of ncRNA-directed chromatin modification were first apparent within the phenomenon of imprinting, whereby only one allele of a gene is expressed from either the maternal or the paternal chromosome In general, imprinted genes are clustered together on chromosomes, suggesting the imprinting mechanism acts upon local chromosome domains rather than individual genes These clusters are also often associated with long ncRNAs whose expression is correlated with the repression of the linked protein-coding gene on the same allele Indeed, detailed analysis has revealed a crucial role for the ncRNAs Kcnqot1 and Igf2r/Air in directing imprinting

Almost all the genes at the Kcnq1 loci are maternally inherited, except the paternally expressed antisense ncRNA Kcnqot1 Transgenic mice with truncated Kcnq1ot fail to silence the adjacent genes, suggesting that Kcnqot1 is crucial to the imprinting of genes on the paternal chromosome It appears that Kcnqot1 is able to direct the trimethylation of lysine 9 H3K9me3 and 27 of histone 3 H3K27me3 to an imprinting centre that overlaps the Kcnqot1 promoter and actually resides within a Kcnq1 sense exon Similar to HOTAIR see above, Eed-Ezh2 Polycomb complexes are recruited to the Kcnq1 loci paternal chromosome, possibly by Kcnqot1, where they may mediate gene silencing through repressive histone methylation A differentially methylated imprinting centre also overlaps the promoter of a long antisense ncRNA Air that is responsible for the silencing of neighbouring genes at the Igf2r locus on the paternal chromosome The presence of allele-specific histone methylation at the Igf2r locus suggests Air also mediates silencing via chromatin modification

Xist and X-chromosome inactivation

The inactivation of a X-chromosome in female placental mammals is directed by one of the earliest and best characterized long ncRNAs, Xist The expression of Xist from the future inactive X-chromosome, and its subsequent coating of the inactive X-chromosome, occurs during early embryonic stem cell differentiation Xist expression is followed by irreversible layers of chromatin modifications that include the loss of the histone H3K9 acetylation and H3K4 methylation that are associated with active chromatin, and the induction of repressive chromatin modifications including H4 hypoacetylation, H3K27 trimethylation, H3K9 hypermethylation and H4K20 monomethylation as well as H2AK119 monoubiquitylation These modifications coincide with the transcriptional silencing of the X-linked genes Xist RNA also localises the histone variant macroH2A to the inactive X–chromosome There are additional ncRNAs that are also present at the Xist loci, including an antisense transcript Tsix, which is expressed from the future active chromosome and able to repress Xist expression by the generation of endogenous siRNA Together these ncRNAs ensure that only one X-chromosome is active in female mammals

Telomeric non-coding RNAs

Telomeres form the terminal region of mammalian chromosomes and are essential for stability and aging and play central roles in diseases such as cancer Telomeres have been long considered transcriptionally inert DNA-protein complexes until it was recently shown that telomeric repeats may be transcribed as telomeric RNAs TelRNAs or telomeric repeat-containing RNAs These ncRNAs are heterogeneous in length, transcribed from several sub-telomeric loci and physically localise to telomeres Their association with chromatin, which suggests an involvement in regulating telomere specific heterochromatin modifications, is repressed by SMG proteins that protect chromosome ends from telomere loss In addition, TelRNAs block telomerase activity in vitro and may therefore regulate telomerase activity Although early, these studies suggest an involvement for telomeric ncRNAs in various aspects of telomere biology

In aging and disease

Recent recognition that long ncRNAs function in various aspects of cell biology has focused increasing attention on their potential to contribute towards disease etiology According to LncRNAWiki, many lncRNAs are correlated with human diseases, especially cancer A handful of studies have implicated long ncRNAs in a variety of disease states and support an involvement and co-operation in neurological disease and cancer

The first published report of an alteration in lncRNA abundance in aging and human neurological disease was provided by Lukiw et al in a study using short post-mortem interval Alzheimer's disease and non-Alzheimer's dementia NAD tissues; this early work was based on the prior identification of a primate brain-specific cytoplasmic transcript of the Alu repeat family by Watson and Sutcliffe in 1987 known as BC200 brain, cytoplasmic, 200 nucleotide

While many association studies have identified unusual expression of long ncRNAs in disease states, there is little understanding of their role in causing disease Expression analyses that compare tumor cells and normal cells have revealed changes in the expression of ncRNAs in several forms of cancer For example, in prostate tumours, PCGEM1 one of two overexpressed ncRNAs is correlated with increased proliferation and colony formation suggesting an involvement in regulating cell growth MALAT1 also known as NEAT2 was originally identified as an abundantly expressed ncRNA that is upregulated during metastasis of early-stage non-small cell lung cancer and its overexpression is an early prognostic marker for poor patient survival rates More recently, the highly conserved mouse homologue of MALAT1 was found to be highly expressed in hepatocellular carcinoma Intronic antisense ncRNAs with expression correlated to the degree of tumor differentiation in prostate cancer samples have also been reported Despite a number of long ncRNAs having aberrant expression in cancer, their function and potential role in tumourogenesis is relatively unknown For example, the ncRNAs HIS-1 and BIC have been implicated in cancer development and growth control, but their function in normal cells is unknown In addition to cancer, ncRNAs also exhibit aberrant expression in other disease states Overexpression of PRINS is associated with psoriasis susceptibility, with PRINS expression being elevated in the uninvolved epidermis of psoriatic patients compared with both psoriatic lesions and healthy epidermis

Genome-wide profiling revealed that many transcribed non-coding ultraconserved regions exhibit distinct profiles in various human cancer states An analysis of chronic lymphocytic leukaemia, colorectal carcinoma and hepatocellular carcinoma found that all three cancers exhibited aberrant expression profiles for ultraconserved ncRNAs relative to normal cells Further analysis of one ultraconserved ncRNA suggested it behaved like an oncogene by mitigating apoptosis and subsequently expanding the number of malignant cells in colorectal cancers Many of these transcribed ultraconserved sites that exhibit distinct signatures in cancer are found at fragile sites and genomic regions associated with cancer It seems likely that the aberrant expression of these ultraconserved ncRNAs within malignant processes results from important functions they fulfil in normal human development

Recently, a number of association studies examining single nucleotide polymorphisms SNPs associated with disease states have been mapped to long ncRNAs For example, SNPs that identified a susceptibility locus for myocardial infarction mapped to a long ncRNA, MIAT myocardial infarction associated transcript Likewise, genome-wide association studies identified a region associated with coronary artery disease that encompassed a long ncRNA, ANRIL ANRIL is expressed in tissues and cell types affected by atherosclerosis and its altered expression is associated with a high-risk haplotype for coronary artery disease

The complexity of the transcriptome, and our evolving understanding of its structure may inform a reinterpretation of the functional basis for many natural polymorphisms associated with disease states Many SNPs associated with certain disease conditions are found within non-coding regions and the complex networks of non-coding transcription within these regions make it particularly difficult to elucidate the functional effects of polymorphisms For example, a SNP both within the truncated form of ZFAT and the promoter of an antisense transcript increases the expression of ZFAT not through increasing the mRNA stability, but rather by repressing the expression of the antisense transcript

The ability of long ncRNAs to regulate associated protein-coding genes may contribute to disease if misexpression of a long ncRNA deregulates a protein coding gene with clinical significance In similar manner, an antisense long ncRNA that regulates the expression of the sense BACE1 gene, a crucial enzyme in Alzheimer’s disease etiology, exhibits elevated expression in several regions of the brain in individuals with Alzheimer's disease Alteration of the expression of ncRNAs may also mediate changes at an epigenetic level to affect gene expression and contribute to disease aetiology For example, the induction of an antisense transcript by a genetic mutation led to DNA methylation and silencing of sense genes, causing ß-thalassemia in a patient

See also

  • Biotechnology portal
  • List of long non-coding RNA databases


  1. ^ Perkel JM June 2013 "Visiting "noncodarnia"" BioTechniques paper 54 6: 301, 303–4 doi:102144/000114037 PMID 23750541 "We're calling long noncoding RNAs a class, when actually the only definition is that they are longer than 200 bp," says Ana Marques, a Research Fellow at the University of Oxford who uses evolutionary approaches to understand lncRNA function 
  2. ^ Ma L, Bajic VB, Zhang Z June 2013 "On the classification of long non-coding RNAs" RNA Biology 10 6: 925–33 doi:104161/rna24604 PMC 4111732  PMID 23696037 
  3. ^ a b Kapranov P, Cheng J, Dike S, Nix DA, Duttagupta R, Willingham AT, Stadler PF, Hertel J, Hackermüller J, Hofacker IL, Bell I, Cheung E, Drenkow J, Dumais E, Patel S, Helt G, Ganesh M, Ghosh S, Piccolboni A, Sementchenko V, Tammana H, Gingeras TR June 2007 "RNA maps reveal new RNA classes and a possible function for pervasive transcription" Science 316 5830: 1484–8 Bibcode:2007Sci3161484K doi:101126/science1138341 PMID 17510325 
  4. ^ a b c d Carninci P, Kasukawa T, Katayama S, Gough J, Frith MC, Maeda N, et al September 2005 "The transcriptional landscape of the mammalian genome" Science 309 5740: 1559–63 Bibcode:2005Sci3091559F doi:101126/science1112014 PMID 16141072 
  5. ^ Cheng J, Kapranov P, Drenkow J, Dike S, Brubaker S, Patel S, Long J, Stern D, Tammana H, Helt G, Sementchenko V, Piccolboni A, Bekiranov S, Bailey DK, Ganesh M, Ghosh S, Bell I, Gerhard DS, Gingeras TR May 2005 "Transcriptional maps of 10 human chromosomes at 5-nucleotide resolution" Science 308 5725: 1149–54 Bibcode:2005Sci3081149C doi:101126/science1108625 PMID 15790807 
  6. ^ Necsulea A, Soumillon M, Warnefors M, Liechti A, Daish T, Zeller U, Baker JC, Grützner F, Kaessmann H January 2014 "The evolution of lncRNA repertoires and expression patterns in tetrapods" Nature 505 7485: 635–40 Bibcode:2014Natur505635N doi:101038/nature12943 PMID 24463510 
  7. ^ a b c Derrien T, Johnson R, Bussotti G, Tanzer A, Djebali S, Tilgner H, Guernec G, Martin D, Merkel A, Knowles DG, Lagarde J, Veeravalli L, Ruan X, Ruan Y, Lassmann T, Carninci P, Brown JB, Lipovich L, Gonzalez JM, Thomas M, Davis CA, Shiekhattar R, Gingeras TR, Hubbard TJ, Notredame C, Harrow J, Guigó R September 2012 "The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression" Genome Research 22 9: 1775–89 doi:101101/gr132159111 PMC 3431493  PMID 22955988 
  8. ^ Hon CC, Ramilowski JA, Harshbarger J, Bertin N, Rackham OJ, Gough J, Denisenko E, Schmeier S, Poulsen TM, Severin J, Lizio M, Kawaji H, Kasukawa T, Itoh M, Burroughs AM, Noma S, Djebali S, Alam T, Medvedeva YA, Testa AC, Lipovich L, Yip CW, Abugessaisa I, Mendez M, Hasegawa A, Tang D, Lassmann T, Heutink P, Babina M, Wells CA, Kojima S, Nakamura Y, Suzuki H, Daub CO, de Hoon MJ, Arner E, Hayashizaki Y, Carninci P, Forrest AR March 2017 "An atlas of human long non-coding RNAs with accurate 5' ends" Nature 543 7644: 199–204 Bibcode:2017Natur543199H doi:101038/nature21374 PMID 28241135 
  9. ^ a b Cabili MN, Trapnell C, Goff L, Koziol M, Tazon-Vega B, Regev A, Rinn JL September 2011 "Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses" Genes & Development 25 18: 1915–27 doi:101101/gad17446611 PMC 3185964  PMID 21890647 
  10. ^ Ravasi T, Suzuki H, Pang KC, Katayama S, Furuno M, Okunishi R, Fukuda S, Ru K, Frith MC, Gongora MM, Grimmond SM, Hume DA, Hayashizaki Y, Mattick JS January 2006 "Experimental validation of the regulated expression of large numbers of non-coding RNAs from the mouse genome" Genome Research 16 1: 11–9 doi:101101/gr4200206 PMC 1356124  PMID 16344565 
  11. ^ Yunusov D, Anderson L, DaSilva LF, Wysocka J, Ezashi T, Roberts RM, Verjovski-Almeida S September 2016 "HIPSTR and thousands of lncRNAs are heterogeneously expressed in human embryos, primordial germ cells and stable cell lines" Scientific Reports 6: 32753 Bibcode:2016NatSR632753Y doi:101038/srep32753 PMC 5015059  PMID 27605307 
  12. ^ Yan L, Yang M, Guo H, Yang L, Wu J, Li R, Liu P, Lian Y, Zheng X, Yan J, Huang J, Li M, Wu X, Wen L, Lao K, Li R, Qiao J, Tang F September 2013 "Single-cell RNA-Seq profiling of human preimplantation embryos and embryonic stem cells" Nature Structural & Molecular Biology 20 9: 1131–9 doi:101038/nsmb2660 PMID 23934149 
  13. ^ Liu SJ, Nowakowski TJ, Pollen AA, Lui JH, Horlbeck MA, Attenello FJ, He D, Weissman JS, Kriegstein AR, Diaz AA, Lim DA April 2016 "Single-cell analysis of long non-coding RNAs in the developing human neocortex" Genome Biology 17: 67 doi:101186/s13059-016-0932-1 PMC 4831157  PMID 27081004 
  14. ^ Paytuví Gallart A, Hermoso Pulido A, Anzar Martínez de Lagrán I, Sanseverino W, Aiese Cigliano R January 2016 "GREENC: a Wiki-based database of plant lncRNAs" Nucleic Acids Research 44 D1: D1161–6 doi:101093/nar/gkv1215 PMC 4702861  PMID 26578586 
  15. ^ Kapranov P, Willingham AT, Gingeras TR June 2007 "Genome-wide transcription and the implications for genomic organization" Nature Reviews Genetics 8 6: 413–23 doi:101038/nrg2083 PMID 17486121 
  16. ^ Birney E, Stamatoyannopoulos JA, Dutta A, Guigó R, Gingeras TR, Margulies EH, et al June 2007 "Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project" Nature 447 7146: 799–816 Bibcode:2007Natur447799B doi:101038/nature05874 PMC 2212820  PMID 17571346 
  17. ^ Anderson DM, Anderson KM, Chang CL, Makarewich CA, Nelson BR, McAnally JR, Kasaragod P, Shelton JM, Liou J, Bassel-Duby R, Olson EN February 2015 "A micropeptide encoded by a putative long noncoding RNA regulates muscle performance" Cell 160 4: 595–606 doi:101016/jcell201501009 PMC 4356254  PMID 25640239 
  18. ^ Matsumoto A, Pasut A, Matsumoto M, Yamashita R, Fung J, Monteleone E, Saghatelian A, Nakayama KI, Clohessy JG, Pandolfi PP January 2017 "mTORC1 and muscle regeneration are regulated by the LINC00961-encoded SPAR polypeptide" Nature 541 7636: 228–232 Bibcode:2017Natur541228M doi:101038/nature21034 PMID 28024296 
  19. ^ Pauli A, Norris ML, Valen E, Chew GL, Gagnon JA, Zimmerman S, Mitchell A, Ma J, Dubrulle J, Reyon D, Tsai SQ, Joung JK, Saghatelian A, Schier AF February 2014 "Toddler: an embryonic signal that promotes cell movement via Apelin receptors" Science 343 6172: 1248636 doi:101126/science1248636 PMC 4107353  PMID 24407481 
  20. ^ Ingolia NT, Lareau LF, Weissman JS November 2011 "Ribosome profiling of mouse embryonic stem cells reveals the complexity and dynamics of mammalian proteomes" Cell 147 4: 789–802 doi:101016/jcell201110002 PMC 3225288  PMID 22056041 
  21. ^ a b Ji Z, Song R, Regev A, Struhl K December 2015 "Many lncRNAs, 5'UTRs, and pseudogenes are translated and some are likely to express functional proteins" eLife 4: e08890 doi:107554/eLife08890 PMC 4739776  PMID 26687005 
  22. ^ Guttman M, Russell P, Ingolia NT, Weissman JS, Lander ES July 2013 "Ribosome profiling provides evidence that large noncoding RNAs do not encode proteins" Cell 154 1: 240–51 doi:101016/jcell201306009 PMC 3756563  PMID 23810193 
  23. ^ Guttman M, Amit I, Garber M, French C, Lin MF, Feldser D, Huarte M, Zuk O, Carey BW, Cassady JP, Cabili MN, Jaenisch R, Mikkelsen TS, Jacks T, Hacohen N, Bernstein BE, Kellis M, Regev A, Rinn JL, Lander ES March 2009 "Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals" Nature 458 7235: 223–7 Bibcode:2009Natur458223G doi:101038/nature07672 PMC 2754849  PMID 19182780 
  24. ^ Ponjavic J, Ponting CP, Lunter G May 2007 "Functionality or transcriptional noise Evidence for selection within long noncoding RNAs" Genome Research 17 5: 556–65 doi:101101/gr6036807 PMC 1855172  PMID 17387145 
  25. ^ Haerty W, Ponting CP May 2013 "Mutations within lncRNAs are effectively selected against in fruitfly but not in human" Genome Biology 14 5: R49 doi:101186/gb-2013-14-5-r49 PMC 4053968  PMID 23710818 
  26. ^ Washietl S, Kellis M, Garber M April 2014 "Evolutionary dynamics and tissue specificity of human long noncoding RNAs in six mammals" Genome Research 24 4: 616–28 doi:101101/gr165035113 PMC 3975061  PMID 24429298 
  27. ^ Kutter C, Watt S, Stefflova K, Wilson MD, Goncalves A, Ponting CP, Odom DT, Marques AC 2012 "Rapid turnover of long noncoding RNAs and the evolution of gene expression" PLoS Genetics 8 7: e1002841 doi:101371/journalpgen1002841 PMC 3406015  PMID 22844254 
  28. ^ Necsulea A, Soumillon M, Warnefors M, Liechti A, Daish T, Zeller U, Baker JC, Grützner F, Kaessmann H January 2014 "The evolution of lncRNA repertoires and expression patterns in tetrapods" Nature 505 7485: 635–40 Bibcode:2014Natur505635N doi:101038/nature12943 PMID 24463510 
  29. ^ Brosius J May 2005 "Waste not, want not--transcript excess in multicellular eukaryotes" Trends in Genetics 21 5: 287–8 doi:101016/jtig200502014 PMID 15851065 
  30. ^ Struhl K February 2007 "Transcriptional noise and the fidelity of initiation by RNA polymerase II" Nature Structural & Molecular Biology 14 2: 103–5 doi:101038/nsmb0207-103 PMID 17277804 
  31. ^ Palazzo AF, Lee ES 2015-01-26 "Non-coding RNA: what is functional and what is junk" Frontiers in Genetics 6: 2 doi:103389/fgene201500002 PMC 4306305  PMID 25674102 
  32. ^ Kapusta A, Feschotte C October 2014 "Volatile evolution of long noncoding RNA repertoires: mechanisms and biological implications" Trends in Genetics 30 10: 439–52 doi:101016/jtig201408004 PMC 4464757  PMID 25218058 
  33. ^ Chen J, Shishkin AA, Zhu X, Kadri S, Maza I, Guttman M, Hanna JH, Regev A, Garber M February 2016 "Evolutionary analysis across mammals reveals distinct classes of long non-coding RNAs" Genome Biology 17: 19 doi:101186/s13059-016-0880-9 PMC 4739325  PMID 26838501 
  34. ^ Ulitsky I October 2016 "Evolution to the rescue: using comparative genomics to understand long non-coding RNAs" Nature Reviews Genetics 17 10: 601–14 doi:101038/nrg201685 PMID 27573374 
  35. ^ Johnsson P, Lipovich L, Grandér D, Morris KV March 2014 "Evolutionary conservation of long non-coding RNAs; sequence, structure, function" Biochimica et Biophysica Acta 1840 3: 1063–71 doi:101016/jbbagen201310035 PMC 3909678  PMID 24184936 
  36. ^ Rivas E, Clements J, Eddy SR January 2017 "A statistical test for conserved RNA structure shows lack of evidence for structure in lncRNAs" Nature Methods 14 1: 45–48 doi:101038/nmeth4066 PMC 5554622  PMID 27819659 
  37. ^ Mercer TR, Dinger ME, Mattick JS March 2009 "Long non-coding RNAs: insights into functions" Nature Reviews Genetics 10 3: 155–9 doi:101038/nrg2521 PMID 19188922 
  38. ^ Dinger ME, Amaral PP, Mercer TR, Mattick JS November 2009 "Pervasive transcription of the eukaryotic genome: functional indices and conceptual implications" Briefings in Functional Genomics & Proteomics 8 6: 407–23 doi:101093/bfgp/elp038 PMID 19770204 
  39. ^ Amaral PP, Clark MB, Gascoigne DK, Dinger ME, Mattick JS January 2011 "lncRNAdb: a reference database for long noncoding RNAs" Nucleic Acids Research 39 Database issue: D146–51 doi:101093/nar/gkq1138 PMC 3013714  PMID 21112873 
  40. ^ Quek XC, Thomson DW, Maag JL, Bartonicek N, Signal B, Clark MB, Gloss BS, Dinger ME January 2015 "lncRNAdb v20: expanding the reference database for functional long noncoding RNAs" Nucleic Acids Research 43 Database issue: D168–73 doi:101093/nar/gku988 PMC 4384040  PMID 25332394 
  41. ^ a b Ma L, Li A, Zou D, Xu X, Xia L, Yu J, Bajic VB, Zhang Z January 2015 "LncRNAWiki: harnessing community knowledge in collaborative curation of human long non-coding RNAs" Nucleic Acids Research 43 Database issue: D187–92 doi:101093/nar/gku1167 PMC 4383965  PMID 25399417 
  42. ^ Smith JE, Alvarez-Dominguez JR, Kline N, Huynh NJ, Geisler S, Hu W, Coller J, Baker KE June 2014 "Translation of small open reading frames within unannotated RNA transcripts in Saccharomyces cerevisiae" Cell Reports 7 6: 1858–66 doi:101016/jcelrep201405023 PMID 24931603 
  43. ^ a b Goodrich JA, Kugel JF August 2006 "Non-coding-RNA regulators of RNA polymerase II transcription" Nature Reviews Molecular Cell Biology 7 8: 612–6 doi:101038/nrm1946 PMID 16723972 
  44. ^ a b Feng J, Bi C, Clark BS, Mady R, Shah P, Kohtz JD June 2006 "The Evf-2 noncoding RNA is transcribed from the Dlx-5/6 ultraconserved region and functions as a Dlx-2 transcriptional coactivator" Genes & Development 20 11: 1470–84 doi:101101/gad1416106 PMC 1475760  PMID 16705037 
  45. ^ Panganiban G, Rubenstein JL October 2002 "Developmental functions of the Distal-less/Dlx homeobox genes" Development 129 19: 4371–86 PMID 12223397 
  46. ^ Pennacchio LA, Ahituv N, Moses AM, Prabhakar S, Nobrega MA, Shoukry M, Minovitsky S, Dubchak I, Holt A, Lewis KD, Plajzer-Frick I, Akiyama J, De Val S, Afzal V, Black BL, Couronne O, Eisen MB, Visel A, Rubin EM November 2006 "In vivo enhancer analysis of human conserved non-coding sequences" Nature 444 7118: 499–502 Bibcode:2006Natur444499P doi:101038/nature05295 PMID 17086198 
  47. ^ Visel A, Prabhakar S, Akiyama JA, Shoukry M, Lewis KD, Holt A, Plajzer-Frick I, Afzal V, Rubin EM, Pennacchio LA February 2008 "Ultraconservation identifies a small subset of extremely constrained developmental enhancers" Nature Genetics 40 2: 158–60 doi:101038/ng200755 PMC 2647775  PMID 18176564 
  48. ^ Pibouin L, Villaudy J, Ferbus D, Muleris M, Prospéri MT, Remvikos Y, Goubin G February 2002 "Cloning of the mRNA of overexpression in colon carcinoma-1: a sequence overexpressed in a subset of colon carcinomas" Cancer Genetics and Cytogenetics 133 1: 55–60 doi:101016/S0165-46080100634-3 PMID 11890990 
  49. ^ a b c Calin GA, Liu CG, Ferracin M, Hyslop T, Spizzo R, Sevignani C, Fabbri M, Cimmino A, Lee EJ, Wojcik SE, Shimizu M, Tili E, Rossi S, Taccioli C, Pichiorri F, Liu X, Zupo S, Herlea V, Gramantieri L, Lanza G, Alder H, Rassenti L, Volinia S, Schmittgen TD, Kipps TJ, Negrini M, Croce CM September 2007 "Ultraconserved regions encoding ncRNAs are altered in human leukemias and carcinomas" Cancer Cell 12 3: 215–29 doi:101016/jccr200707027 PMID 17785203 
  50. ^ Luo S, Lu JY, Liu L, Yin Y, Chen C, Han X, Wu B, Xu R, Liu W, Yan P, Shao W, Lu Z, Li H, Na J, Tang F, Wang J, Zhang YE, Shen X May 2016 "Divergent lncRNAs Regulate Gene Expression and Lineage Differentiation in Pluripotent Cells" Cell Stem Cell 18 5: 637–52 doi:101016/jstem201601024 PMID 26996597 
  51. ^ Wang X, Arai S, Song X, Reichart D, Du K, Pascual G, Tempst P, Rosenfeld MG, Glass CK, Kurokawa R July 2008 "Induced ncRNAs allosterically modify RNA-binding proteins in cis to inhibit transcription" Nature 454 7200: 126–30 Bibcode:2008Natur454126W doi:101038/nature06992 PMC 2823488  PMID 18509338 
  52. ^ Adelman K, Egan E March 2017 "Non-coding RNA: More uses for genomic junk" Nature 543 7644: 183–185 Bibcode:2017Natur543183A doi:101038/543183a PMID 28277509 
  53. ^ Halley P, Kadakkuzha BM, Faghihi MA, Magistri M, Zeier Z, Khorkova O, Coito C, Hsiao J, Lawrence M, Wahlestedt C January 2014 "Regulation of the apolipoprotein gene cluster by a long noncoding RNA" Cell Reports 6 1: 222–30 doi:101016/jcelrep201312015 PMC 3924898  PMID 24388749 
  54. ^ Reinius B, Shi C, Hengshuo L, Sandhu KS, Radomska KJ, Rosen GD, Lu L, Kullander K, Williams RW, Jazin E November 2010 "Female-biased expression of long non-coding RNAs in domains that escape X-inactivation in mouse" BMC Genomics 11: 614 doi:101186/1471-2164-11-614 PMC 3091755  PMID 21047393 
  55. ^ Martianov I, Ramadass A, Serra Barros A, Chow N, Akoulitchev A February 2007 "Repression of the human dihydrofolate reductase gene by a non-coding interfering transcript" Nature 445 7128: 666–70 doi:101038/nature05519 PMID 17237763 
  56. ^ Lee JS, Burkholder GD, Latimer LJ, Haug BL, Braun RP February 1987 "A monoclonal antibody to triplex DNA binds to eucaryotic chromosomes" Nucleic Acids Research 15 3: 1047–61 doi:101093/nar/1531047 PMC 340507  PMID 2434928 
  57. ^ a b Kwek KY, Murphy S, Furger A, Thomas B, O'Gorman W, Kimura H, Proudfoot NJ, Akoulitchev A November 2002 "U1 snRNA associates with TFIIH and regulates transcriptional initiation" Nature Structural Biology 9 11: 800–5 doi:101038/nsb862 PMID 12389039 
  58. ^ Yang S, Tutton S, Pierce E, Yoon K November 2001 "Specific double-stranded RNA interference in undifferentiated mouse embryonic stem cells" Molecular and Cellular Biology 21 22: 7807–16 doi:101128/MCB21227807-78162001 PMC 99950  PMID 11604515 
  59. ^ Yik JH, Chen R, Nishimura R, Jennings JL, Link AJ, Zhou Q October 2003 "Inhibition of P-TEFb CDK9/Cyclin T kinase and RNA polymerase II transcription by the coordinated actions of HEXIM1 and 7SK snRNA" Molecular Cell 12 4: 971–82 doi:101016/S1097-27650300388-5 PMID 14580347 
  60. ^ Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, et al February 2001 "Initial sequencing and analysis of the human genome" Nature 409 6822: 860–921 doi:101038/35057062 PMID 11237011 
  61. ^ Waterston RH, Lindblad-Toh K, Birney E, Rogers J, Abril JF, Agarwal P, et al December 2002 "Initial sequencing and comparative analysis of the mouse genome" Nature 420 6915: 520–62 Bibcode:2002Natur420520W doi:101038/nature01262 PMID 12466850 
  62. ^ Liu WM, Chu WM, Choudary PV, Schmid CW May 1995 "Cell stress and translational inhibitors transiently increase the abundance of mammalian SINE transcripts" Nucleic Acids Research 23 10: 1758–65 doi:101093/nar/23101758 PMC 306933  PMID 7784180 
  63. ^ a b Allen E, Xie Z, Gustafson AM, Sung GH, Spatafora JW, Carrington JC December 2004 "Evolution of microRNA genes by inverted duplication of target gene sequences in Arabidopsis thaliana" Nature Genetics 36 12: 1282–90 doi:101038/ng1478 PMID 15565108 
  64. ^ a b Espinoza CA, Allen TA, Hieb AR, Kugel JF, Goodrich JA September 2004 "B2 RNA binds directly to RNA polymerase II to repress transcript synthesis" Nature Structural & Molecular Biology 11 9: 822–9 doi:101038/nsmb812 PMID 15300239 
  65. ^ Espinoza CA, Goodrich JA, Kugel JF April 2007 "Characterization of the structure, function, and mechanism of B2 RNA, an ncRNA repressor of RNA polymerase II transcription" Rna 13 4: 583–96 doi:101261/rna310307 PMC 1831867  PMID 17307818 
  66. ^ a b c d e f Mariner PD, Walters RD, Espinoza CA, Drullinger LF, Wagner SD, Kugel JF, Goodrich JA February 2008 "Human Alu RNA is a modular transacting repressor of mRNA transcription during heat shock" Molecular Cell 29 4: 499–509 doi:101016/jmolcel200712013 PMID 18313387 
  67. ^ Shamovsky I, Nudler E February 2008 "Modular RNA heats up" Molecular Cell 29 4: 415–7 doi:101016/jmolcel200802001 PMID 18313380 
  68. ^ Mattick JS October 2003 "Challenging the dogma: the hidden layer of non-protein-coding RNAs in complex organisms" BioEssays 25 10: 930–9 doi:101002/bies10332 PMID 14505360 
  69. ^ Mohammad F, Pandey RR, Nagano T, Chakalova L, Mondal T, Fraser P, Kanduri C June 2008 "Kcnq1ot1/Lit1 noncoding RNA mediates transcriptional silencing by targeting to the perinucleolar region" Molecular and Cellular Biology 28 11: 3713–28 doi:101128/MCB02263-07 PMC 2423283  PMID 18299392 
  70. ^ Wutz A, Rasmussen TP, Jaenisch R February 2002 "Chromosomal silencing and localization are mediated by different domains of Xist RNA" Nature Genetics 30 2: 167–74 doi:101038/ng820 PMID 11780141 
  71. ^ Zearfoss NR, Chan AP, Kloc M, Allen LH, Etkin LD April 2003 "Identification of new Xlsirt family members in the Xenopus laevis oocyte" Mechanisms of Development 120 4: 503–9 doi:101016/S0925-47730200459-8 PMID 12676327 
  72. ^ Singh K, Carey M, Saragosti S, Botchan M 1985 "Expression of enhanced levels of small RNA polymerase III transcripts encoded by the B2 repeats in simian virus 40-transformed mouse cells" Nature 314 6011: 553–6 Bibcode:1985Natur314553S doi:101038/314553a0 PMID 2581137 
  73. ^ Tang RB, Wang HY, Lu HY, Xiong J, Li HH, Qiu XH, Liu HQ February 2005 "Increased level of polymerase III transcribed Alu RNA in hepatocellular carcinoma tissue" Molecular Carcinogenesis 42 2: 93–6 doi:101002/mc20057 PMID 15593371 
  74. ^ a b Shamovsky I, Nudler E October 2006 "Gene control by large noncoding RNAs" Science's STKE 2006 355: pe40 doi:101126/stke3552006pe40 PMID 17018852 
  75. ^ a b Dieci G, Fiorino G, Castelnuovo M, Teichmann M, Pagano A December 2007 "The expanding RNA polymerase III transcriptome" Trends in Genetics 23 12: 614–22 doi:101016/jtig200709001 PMID 17977614 
  76. ^ Pagano JM, Farley BM, McCoig LM, Ryder SP March 2007 "Molecular basis of RNA recognition by the embryonic polarity determinant MEX-5" The Journal of Biological Chemistry 282 12: 8883–94 doi:101074/jbcM700079200 PMID 17264081 
  77. ^ a b Beltran M, Puig I, Peña C, García JM, Alvarez AB, Peña R, Bonilla F, de Herreros AG March 2008 "A natural antisense transcript regulates Zeb2/Sip1 gene expression during Snail1-induced epithelial-mesenchymal transition" Genes & Development 22 6: 756–69 doi:101101/gad455708 PMC 2275429  PMID 18347095 
  78. ^ Munroe SH, Lazar MA November 1991 "Inhibition of c-erbA mRNA splicing by a naturally occurring antisense RNA" The Journal of Biological Chemistry 266 33: 22083–6 PMID 1657988 
  79. ^ Tiedge H, Chen W, Brosius J June 1993 "Primary structure, neural-specific expression, and dendritic location of human BC200 RNA" The Journal of Neuroscience 13 6: 2382–90 PMID 7684772 
  80. ^ Tiedge H, Fremeau RT, Weinstock PH, Arancio O, Brosius J March 1991 "Dendritic location of neural BC1 RNA" Proceedings of the National Academy of Sciences of the United States of America 88 6: 2093–7 Bibcode:1991PNAS882093T doi:101073/pnas8862093 PMC 51175  PMID 1706516 
  81. ^ Muslimov IA, Banker G, Brosius J, Tiedge H June 1998 "Activity-dependent regulation of dendritic BC1 RNA in hippocampal neurons in culture" The Journal of Cell Biology 141 7: 1601–11 doi:101083/jcb14171601 PMC 1828539  PMID 9647652 
  82. ^ Wang H, Iacoangeli A, Lin D, Williams K, Denman RB, Hellen CU, Tiedge H December 2005 "Dendritic BC1 RNA in translational control mechanisms" The Journal of Cell Biology 171 5: 811–21 doi:101083/jcb200506006 PMC 1828541  PMID 16330711 
  83. ^ Centonze D, Rossi S, Napoli I, Mercaldo V, Lacoux C, Ferrari F, Ciotti MT, De Chiara V, Prosperetti C, Maccarrone M, Fezza F, Calabresi P, Bernardi G, Bagni C August 2007 "The brain cytoplasmic RNA BC1 regulates dopamine D2 receptor-mediated transmission in the striatum" The Journal of Neuroscience 27 33: 8885–92 doi:101523/JNEUROSCI0548-072007 PMID 17699670 
  84. ^ Lewejohann L, Skryabin BV, Sachser N, Prehn C, Heiduschka P, Thanos S, Jordan U, Dell'Omo G, Vyssotski AL, Pleskacheva MG, Lipp HP, Tiedge H, Brosius J, Prior H September 2004 "Role of a neuronal small non-messenger RNA: behavioural alterations in BC1 RNA-deleted mice" Behavioural Brain Research 154 1: 273–89 doi:101016/jbbr200402015 PMID 15302134 
  85. ^ Golden DE, Gerbasi VR, Sontheimer EJ August 2008 "An inside job for siRNAs" Molecular Cell 31 3: 309–12 doi:101016/jmolcel200807008 PMC 2675693  PMID 18691963 
  86. ^ Czech B, Malone CD, Zhou R, Stark A, Schlingeheyde C, Dus M, Perrimon N, Kellis M, Wohlschlegel JA, Sachidanandam R, Hannon GJ, Brennecke J June 2008 "An endogenous small interfering RNA pathway in Drosophila" Nature 453 7196: 798–802 Bibcode:2008Natur453798C doi:101038/nature07007 PMC 2895258  PMID 18463631 
  87. ^ a b Ogawa Y, Sun BK, Lee JT June 2008 "Intersection of the RNA interference and X-inactivation pathways" Science 320 5881: 1336–41 Bibcode:2008Sci3201336O doi:101126/science1157676 PMC 2584363  PMID 18535243 
  88. ^ Kiefer JC April 2007 "Epigenetics in development" Developmental Dynamics 236 4: 1144–56 doi:101002/dvdy21094 PMID 17304537 
  89. ^ a b Mikkelsen TS, Ku M, Jaffe DB, Issac B, Lieberman E, Giannoukos G, Alvarez P, Brockman W, Kim TK, Koche RP, Lee W, Mendenhall E, O'Donovan A, Presser A, Russ C, Xie X, Meissner A, Wernig M, Jaenisch R, Nusbaum C, Lander ES, Bernstein BE August 2007 "Genome-wide maps of chromatin state in pluripotent and lineage-committed cells" Nature 448 7153: 553–60 Bibcode:2007Natur448553M doi:101038/nature06008 PMC 2921165  PMID 17603471 
  90. ^ Nickerson JA, Krochmalnic G, Wan KM, Penman S January 1989 "Chromatin architecture and nuclear RNA" Proceedings of the National Academy of Sciences of the United States of America 86 1: 177–81 Bibcode:1989PNAS86177N doi:101073/pnas861177 PMC 286427  PMID 2911567 
  91. ^ Rodríguez-Campos A, Azorín F November 2007 "RNA is an integral component of chromatin that contributes to its structural organization" PLOS One 2 11: e1182 Bibcode:2007PLoSO21182R doi:101371/journalpone0001182 PMC 2063516  PMID 18000552 
  92. ^ Chen X, Xu H, Yuan P, Fang F, Huss M, Vega VB, Wong E, Orlov YL, Zhang W, Jiang J, Loh YH, Yeo HC, Yeo ZX, Narang V, Govindarajan KR, Leong B, Shahab A, Ruan Y, Bourque G, Sung WK, Clarke ND, Wei CL, Ng HH June 2008 "Integration of external signaling pathways with the core transcriptional network in embryonic stem cells" Cell 133 6: 1106–17 doi:101016/jcell200804043 PMID 18555785 
  93. ^ a b c Rinn JL, Kertesz M, Wang JK, Squazzo SL, Xu X, Brugmann SA, Goodnough LH, Helms JA, Farnham PJ, Segal E, Chang HY June 2007 "Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs" Cell 129 7: 1311–23 doi:101016/jcell200705022 PMC 2084369  PMID 17604720 
  94. ^ a b Sanchez-Elsner T, Gou D, Kremmer E, Sauer F February 2006 "Noncoding RNAs of trithorax response elements recruit Drosophila Ash1 to Ultrabithorax" Science 311 5764: 1118–23 Bibcode:2006Sci3111118S doi:101126/science1117705 PMID 16497925 
  95. ^ Mazo A, Hodgson JW, Petruk S, Sedkov Y, Brock HW August 2007 "Transcriptional interference: an unexpected layer of complexity in gene regulation" Journal of Cell Science 120 Pt 16: 2755–61 doi:101242/jcs007633 PMID 17690303 
  96. ^ Denisenko O, Shnyreva M, Suzuki H, Bomsztyk K October 1998 "Point mutations in the WD40 domain of Eed block its interaction with Ezh2" Molecular and Cellular Biology 18 10: 5634–42 PMC 109149  PMID 9742080 
  97. ^ Katayama S, Tomaru Y, Kasukawa T, Waki K, Nakanishi M, Nakamura M, Nishida H, Yap CC, Suzuki M, Kawai J, Suzuki H, Carninci P, Hayashizaki Y, Wells C, Frith M, Ravasi T, Pang KC, Hallinan J, Mattick J, Hume DA, Lipovich L, Batalov S, Engström PG, Mizuno Y, Faghihi MA, Sandelin A, Chalk AM, Mottagui-Tabar S, Liang Z, Lenhard B, Wahlestedt C September 2005 "Antisense transcription in the mammalian transcriptome" Science 309 5740: 1564–6 Bibcode:2005Sci3091564R doi:101126/science1112009 PMID 16141073 
  98. ^ a b c Yu W, Gius D, Onyango P, Muldoon-Jacobs K, Karp J, Feinberg AP, Cui H January 2008 "Epigenetic silencing of tumour suppressor gene p15 by its antisense RNA" Nature 451 7175: 202–6 Bibcode:2008Natur451202Y doi:101038/nature06468 PMC 2743558  PMID 18185590 
  99. ^ Pauler FM, Koerner MV, Barlow DP June 2007 "Silencing by imprinted noncoding RNAs: is transcription the answer" Trends in Genetics 23 6: 284–92 doi:101016/jtig200703018 PMC 2847181  PMID 17445943 
  100. ^ Braidotti G, Baubec T, Pauler F, Seidl C, Smrzka O, Stricker S, Yotova I, Barlow DP 2004 "The Air noncoding RNA: an imprinted cis-silencing transcript" Cold Spring Harbor Symposia on Quantitative Biology 69: 55–66 doi:101101/sqb20046955 PMC 2847179  PMID 16117633 
  101. ^ Mitsuya K, Meguro M, Lee MP, Katoh M, Schulz TC, Kugoh H, Yoshida MA, Niikawa N, Feinberg AP, Oshimura M July 1999 "LIT1, an imprinted antisense RNA in the human KvLQT1 locus identified by screening for differentially expressed transcripts using monochromosomal hybrids" Human Molecular Genetics 8 7: 1209–17 doi:101093/hmg/871209 PMID 10369866 
  102. ^ Mancini-Dinardo D, Steele SJ, Levorse JM, Ingram RS, Tilghman SM May 2006 "Elongation of the Kcnq1ot1 transcript is required for genomic imprinting of neighboring genes" Genes & Development 20 10: 1268–82 doi:101101/gad1416906 PMC 1472902  PMID 16702402 
  103. ^ a b Umlauf D, Goto Y, Cao R, Cerqueira F, Wagschal A, Zhang Y, Feil R December 2004 "Imprinting along the Kcnq1 domain on mouse chromosome 7 involves repressive histone methylation and recruitment of Polycomb group complexes" Nature Genetics 36 12: 1296–300 doi:101038/ng1467 PMID 15516932 
  104. ^ Sleutels F, Zwart R, Barlow DP February 2002 "The non-coding Air RNA is required for silencing autosomal imprinted genes" Nature 415 6873: 810–3 doi:101038/415810a PMID 11845212 
  105. ^ Zwart R, Sleutels F, Wutz A, Schinkel AH, Barlow DP September 2001 "Bidirectional action of the Igf2r imprint control element on upstream and downstream imprinted genes" Genes & Development 15 18: 2361–6 doi:101101/gad206201 PMC 312779  PMID 11562346 
  106. ^ Fournier C, Goto Y, Ballestar E, Delaval K, Hever AM, Esteller M, Feil R December 2002 "Allele-specific histone lysine methylation marks regulatory regions at imprinted mouse genes" The EMBO Journal 21 23: 6560–70 doi:101093/emboj/cdf655 PMC 136958  PMID 12456662 
  107. ^ a b Wutz A, Gribnau J October 2007 "X inactivation Xplained" Current Opinion in Genetics & Development 17 5: 387–93 doi:101016/jgde200708001 PMID 17869504 
  108. ^ Morey C, Navarro P, Debrand E, Avner P, Rougeulle C, Clerc P February 2004 "The region 3' to Xist mediates X chromosome counting and H3 Lys-4 dimethylation within the Xist gene" The EMBO Journal 23 3: 594–604 doi:101038/sjemboj7600071 PMC 1271805  PMID 14749728 
  109. ^ Costanzi C, Pehrson JR June 1998 "Histone macroH2A1 is concentrated in the inactive X chromosome of female mammals" Nature 393 6685: 599–601 Bibcode:1998Natur393599C doi:101038/31275 PMID 9634239 
  110. ^ Blasco MA October 2007 "Telomere length, stem cells and aging" Nature Chemical Biology 3 10: 640–9 doi:101038/nchembio200738 PMID 17876321 
  111. ^ a b Schoeftner S, Blasco MA February 2008 "Developmentally regulated transcription of mammalian telomeres by DNA-dependent RNA polymerase II" Nature Cell Biology 10 2: 228–36 doi:101038/ncb1685 PMID 18157120 
  112. ^ a b Azzalin CM, Reichenbach P, Khoriauli L, Giulotto E, Lingner J November 2007 "Telomeric repeat containing RNA and RNA surveillance factors at mammalian chromosome ends" Science 318 5851: 798–801 Bibcode:2007Sci318798A doi:101126/science1147182 PMID 17916692 
  113. ^ Lukiw WJ, Handley P, Wong L, Crapper McLachlan DR June 1992 "BC200 RNA in normal human neocortex, non-Alzheimer dementia NAD, and senile dementia of the Alzheimer type AD" Neurochemical Research 17 6: 591–7 doi:101007/bf00968788 PMID 1603265 
  114. ^ Watson JB, Sutcliffe JG September 1987 "Primate brain-specific cytoplasmic transcript of the Alu repeat family" Molecular and Cellular Biology 7 9: 3324–7 PMC 367971  PMID 2444875 
  115. ^ a b Fu X, Ravindranath L, Tran N, Petrovics G, Srivastava S March 2006 "Regulation of apoptosis by a prostate-specific and prostate cancer-associated noncoding gene, PCGEM1" DNA and Cell Biology 25 3: 135–41 doi:101089/dna200625135 PMID 16569192 
  116. ^ Lin R, Maeda S, Liu C, Karin M, Edgington TS February 2007 "A large noncoding RNA is a marker for murine hepatocellular carcinomas and a spectrum of human carcinomas" Oncogene 26 6: 851–8 doi:101038/sjonc1209846 PMID 16878148 
  117. ^ Reis EM, Nakaya HI, Louro R, Canavez FC, Flatschart AV, Almeida GT, Egidio CM, Paquola AC, Machado AA, Festa F, Yamamoto D, Alvarenga R, da Silva CC, Brito GC, Simon SD, Moreira-Filho CA, Leite KR, Camara-Lopes LH, Campos FS, Gimba E, Vignal GM, El-Dorry H, Sogayar MC, Barcinski MA, da Silva AM, Verjovski-Almeida S August 2004 "Antisense intronic non-coding RNA levels correlate to the degree of tumor differentiation in prostate cancer" Oncogene 23 39: 6684–92 doi:101038/sjonc1207880 PMID 15221013 
  118. ^ Eis PS, Tam W, Sun L, Chadburn A, Li Z, Gomez MF, Lund E, Dahlberg JE March 2005 "Accumulation of miR-155 and BIC RNA in human B cell lymphomas" Proceedings of the National Academy of Sciences of the United States of America 102 10: 3627–32 Bibcode:2005PNAS1023627E doi:101073/pnas0500613102 PMC 552785  PMID 15738415 
  119. ^ Li J, Witte DP, Van Dyke T, Askew DS April 1997 "Expression of the putative proto-oncogene His-1 in normal and neoplastic tissues" The American Journal of Pathology 150 4: 1297–305 PMC 1858164  PMID 9094986 
  120. ^ Sonkoly E, Bata-Csorgo Z, Pivarcsi A, Polyanka H, Kenderessy-Szabo A, Molnar G, Szentpali K, Bari L, Megyeri K, Mandi Y, Dobozy A, Kemeny L, Szell M June 2005 "Identification and characterization of a novel, psoriasis susceptibility-related noncoding RNA gene, PRINS" The Journal of Biological Chemistry 280 25: 24159–67 doi:101074/jbcM501704200 PMID 15855153 
  121. ^ Ishii N, Ozaki K, Sato H, Mizuno H, Saito S, Takahashi A, Miyamoto Y, Ikegawa S, Kamatani N, Hori M, Saito S, Nakamura Y, Tanaka T 2006 "Identification of a novel non-coding RNA, MIAT, that confers risk of myocardial infarction" Journal of Human Genetics 51 12: 1087–99 doi:101007/s10038-006-0070-9 PMID 17066261 
  122. ^ McPherson R, Pertsemlidis A, Kavaslar N, Stewart A, Roberts R, Cox DR, Hinds DA, Pennacchio LA, Tybjaerg-Hansen A, Folsom AR, Boerwinkle E, Hobbs HH, Cohen JC June 2007 "A common allele on chromosome 9 associated with coronary heart disease" Science 316 5830: 1488–91 Bibcode:2007Sci3161488M doi:101126/science1142447 PMC 2711874  PMID 17478681 
  123. ^ Pasmant E, Laurendeau I, Héron D, Vidaud M, Vidaud D, Bièche I April 2007 "Characterization of a germ-line deletion, including the entire INK4/ARF locus, in a melanoma-neural system tumor family: identification of ANRIL, an antisense noncoding RNA whose expression coclusters with ARF" Cancer Research 67 8: 3963–9 doi:101158/0008-5472CAN-06-2004 PMID 17440112 
  124. ^ Broadbent HM, Peden JF, Lorkowski S, Goel A, Ongen H, Green F, Clarke R, Collins R, Franzosi MG, Tognoni G, Seedorf U, Rust S, Eriksson P, Hamsten A, Farrall M, Watkins H March 2008 "Susceptibility to coronary artery disease and diabetes is encoded by distinct, tightly linked SNPs in the ANRIL locus on chromosome 9p" Human Molecular Genetics 17 6: 806–14 doi:101093/hmg/ddm352 PMID 18048406 
  125. ^ a b Jarinova O, Stewart AF, Roberts R, Wells G, Lau P, Naing T, Buerki C, McLean BW, Cook RC, Parker JS, McPherson R October 2009 "Functional analysis of the chromosome 9p213 coronary artery disease risk locus" Arteriosclerosis, Thrombosis, and Vascular Biology 29 10: 1671–7 doi:101161/ATVBAHA109189522 PMID 19592466 
  126. ^ Liu Y, Sanoff HK, Cho H, Burd CE, Torrice C, Mohlke KL, Ibrahim JG, Thomas NE, Sharpless NE April 2009 "INK4/ARF transcript expression is associated with chromosome 9p21 variants linked to atherosclerosis" PLOS One 4 4: e5027 Bibcode:2009PLoSO45027L doi:101371/journalpone0005027 PMC 2660422  PMID 19343170 
  127. ^ Shirasawa S, Harada H, Furugaki K, Akamizu T, Ishikawa N, Ito K, Ito K, Tamai H, Kuma K, Kubota S, Hiratani H, Tsuchiya T, Baba I, Ishikawa M, Tanaka M, Sakai K, Aoki M, Yamamoto K, Sasazuki T October 2004 "SNPs in the promoter of a B cell-specific antisense transcript, SAS-ZFAT, determine susceptibility to autoimmune thyroid disease" Human Molecular Genetics 13 19: 2221–31 doi:101093/hmg/ddh245 PMID 15294872 
  128. ^ Faghihi MA, Modarresi F, Khalil AM, Wood DE, Sahagan BG, Morgan TE, Finch CE, St Laurent G, Kenny PJ, Wahlestedt C July 2008 "Expression of a noncoding RNA is elevated in Alzheimer's disease and drives rapid feed-forward regulation of beta-secretase" Nature Medicine 14 7: 723–30 doi:101038/nm1784 PMC 2826895  PMID 18587408 
  129. ^ Tufarelli C, Stanley JA, Garrick D, Sharpe JA, Ayyub H, Wood WG, Higgs DR June 2003 "Transcription of antisense RNA leading to gene silencing and methylation as a novel cause of human genetic disease" Nature Genetics 34 2: 157–65 doi:101038/ng1157 PMID 12730694 

long non-coding rna, long non-coding rna structure, long non-coding rna synthesis, long non-coding rnas: insights into functions, long noncoding rna cancer, long noncoding rna database, long noncoding rna function, long noncoding rna review, long noncoding rnas regulate adipogenesis, long noncoding rnas: past present and future

Long non-coding RNA Information about

Long non-coding RNA

  • user icon

    Long non-coding RNA beatiful post thanks!


Long non-coding RNA
Long non-coding RNA
Long non-coding RNA viewing the topic.
Long non-coding RNA what, Long non-coding RNA who, Long non-coding RNA explanation

There are excerpts from wikipedia on this article and video

Random Posts

Ralph Neville, 2nd Earl of Westmorland

Ralph Neville, 2nd Earl of Westmorland

Ralph Neville, 2nd Earl of Westmorland 4 April 1406 – 3 November 1484 was an English peer Content...
Mamprusi language

Mamprusi language

The Mamprusi language, Mampruli Mampelle, Ŋmampulli, is a Gur language spoken in northern Ghana by t...
Singapore Changi Airport

Singapore Changi Airport

Singapore Changi Airport IATA: SIN, ICAO: WSSS, or simply Changi Airport, is the primary civili...
Christian Siriano

Christian Siriano

Christian Siriano born November 18, 1985 is an American fashion designer and member of the Council o...