Short interspersed nuclear elementlong interspersed nuclear element, short interspersed nuclear element
Short Interspersed Nuclear Elements SINEs are non-autonomous, non-coding transposable elements TEs that are 50-500 base pairs long The internal regions of SINEs originate from tRNA and remain highly conserved, suggesting positive pressure to preserve structure and function of SINEs While SINEs are present in many species of vertebrates and invertebrates, SINEs are often lineage specific, making them useful markers of divergent evolution between species Copy number variation and mutations in the SINE sequence make it possible to construct phylogenies based on differences in SINEs between species SINEs are also implicated in certain types of genetic disease in humans and other eukaryotes
- 1 Classification and Structure
- 2 Propagation and Regulation
- 3 Effects of SINE Transposition
- 4 Common SINEs
- 5 SINE Diseases
- 6 References
Classification and Structure
SINEs are classified as non-LTR retrotransposons because they do not contain long terminal repeats LTRs There are three types of SINEs common to vertebrates and invertebrates: CORE-SINEs, V-SINEs, and AmnSINEs SINEs have 50-500 base pair internal regions which contain a tRNA-derived segment with A and B boxes that serve as an internal promoter for RNA polymerase III
Propagation and Regulation
SINEs use an RNA intermediate and reverse transcriptase to transpose into new parts of the genome SINEs do not encode a functional reverse transcriptase and have to rely on the molecular machinery of other TEs for transposition SINEs and other nuclear elements rely on the LINE-1 L1 proteins for transposition throughout the genome L1 is transcribed and retrotransposed most frequently in the germ-line and during early development; as a result SINEs move around the genome most during these periods SINE transcription is down-regulated by transcription factors in somatic cells after early development, though stress can cause up-regulation of normally silent SINEs SINEs can be transferred between individuals or species via horizontal transfer though a viral vector
Effects of SINE Transposition
Insertion of a SINE upstream of a coding region may result in exon shuffling or changes to the regulatory region of the gene Insertion of a SINE into the coding sequence of a gene can have deleterious effects and unregulated transposition can cause genetic disease The transposition and recombination of SINEs and other active nuclear elements is thought to be one of the major contributions of genetic diversity between lineages during speciation
Alu elements are the most common SINE in humans, with >1,000,000 copies throughout the genome Alu element copy number differences can be used to distinguish between and construct phylogenies of primate species Canines differ primarily in their abundance of SINEC_Cf repeats throughout the genome, rather than other gene or allele level mutations These dog-specific SINEs may code for a splice acceptor site, altering the sequences that appear as exons or introns in each species
There are >50 human diseases associated with SINEs When inserted near or within the exon, SINEs can cause improper splicing, become coding regions, or change the reading frame, often leading to disease phenotypes in humans and other animals Insertion of Alu elements in the human genome is associated with breast cancer, colon cancer, leukemia, hemophilia, Dent’s Disease, cystic fibrosis, neurofibromatosis, and many others
- ^ a b c Sun, F; Fleurdépine, S; Bousquet-Antonelli, C; Caetano-Anollés, G; Deragon, J 2006 "Common evolutionary trends for SINE RNA structures" Trends in Genetics 23 1: 26–33 doi:101016/jtig200611005 PMID 17126948
- ^ a b c Hancks, D; Kazazian, H 2013 "Active human retrotransposons: variation and disease" Current Opinion in Genetics & Development 22: 191–203 doi:101016/jgde201202006 PMC 3376660
- ^ Wicker, T; Sabot, F; Hau-Van, A; Bennetzen, J; Capy, P; Chaloub, B; Flavell, A; Leroy, P; Morgante, M; Panaud, O 2007 "A unified classification system for eukaryotic transposable elements" Nature 8: 973–982 doi:101038/nrg2165 PMID 17984973
- ^ a b Beauregard, A; Curcio, M; Belfort, M 2008 "Give and take between retrotransposable elements and their hosts" Annual Review of Genetics 42: 587–617 doi:101146/annurevgenet42110807091549 PMC 2665727 PMID 18680436
- ^ a b c Böhne, A; Brunet, F; Galiana-Arnoux, D; Schultheis, C; Volff, J 2008 " Transposable elements as drivers of genomic and biological diversity in vertebrates" Chromosome Research 16: 203–215 doi:101007/s10577-007-1202-6
- ^ a b Wang, W; Kirkness, E 2005 "Short interspersed elements SINEs are a major source of canine genomic diversity" Genome Research 15: 1798–1808 doi:101101/gr3765505 PMC 1356118 PMID 16339378
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