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  • 1
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    Widespread alternative and aberrant splicing revealed by lariat sequencing (2015)
    Oxford University Press
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    Publication Date: 2015-09-30
    Description: Alternative splicing is an important and ancient feature of eukaryotic gene structure, the existence of which has likely facilitated eukaryotic proteome expansions. Here, we have used intron lariat sequencing to generate a comprehensive profile of splicing events in Schizosaccharomyces pombe , amongst the simplest organisms that possess mammalian-like splice site degeneracy. We reveal an unprecedented level of alternative splicing, including alternative splice site selection for over half of all annotated introns, hundreds of novel exon-skipping events, and thousands of novel introns. Moreover, the frequency of these events is far higher than previous estimates, with alternative splice sites on average activated at ~3% the rate of canonical sites. Although a subset of alternative sites are conserved in related species, implying functional potential, the majority are not detectably conserved. Interestingly, the rate of aberrant splicing is inversely related to expression level, with lowly expressed genes more prone to erroneous splicing. Although we validate many events with RNAseq, the proportion of alternative splicing discovered with lariat sequencing is far greater, a difference we attribute to preferential decay of aberrantly spliced transcripts. Together, these data suggest the spliceosome possesses far lower fidelity than previously appreciated, highlighting the potential contributions of alternative splicing in generating novel gene structures.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 2
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    Early origins and evolution of microRNAs and Piwi-interacting RNAs in animals (2008)
    Nature Publishing Group (NPG)
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    Publication Date: 2008-10-03
    Description: In bilaterian animals, such as humans, flies and worms, hundreds of microRNAs (miRNAs), some conserved throughout bilaterian evolution, collectively regulate a substantial fraction of the transcriptome. In addition to miRNAs, other bilaterian small RNAs, known as Piwi-interacting RNAs (piRNAs), protect the genome from transposons. Here we identify small RNAs from animal phyla that diverged before the emergence of the Bilateria. The cnidarian Nematostella vectensis (starlet sea anemone), a close relative to the Bilateria, possesses an extensive repertoire of miRNA genes, two classes of piRNAs and a complement of proteins specific to small-RNA biology comparable to that of humans. The poriferan Amphimedon queenslandica (sponge), one of the simplest animals and a distant relative of the Bilateria, also possesses miRNAs, both classes of piRNAs and a full complement of the small-RNA machinery. Animal miRNA evolution seems to have been relatively dynamic, with precursor sizes and mature miRNA sequences differing greatly between poriferans, cnidarians and bilaterians. Nonetheless, miRNAs and piRNAs have been available as classes of riboregulators to shape gene expression throughout the evolution and radiation of animal phyla.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3837422/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3837422/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grimson, Andrew -- Srivastava, Mansi -- Fahey, Bryony -- Woodcroft, Ben J -- Chiang, H Rosaria -- King, Nicole -- Degnan, Bernard M -- Rokhsar, Daniel S -- Bartel, David P -- R01 GM067031/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2008 Oct 30;455(7217):1193-7. doi: 10.1038/nature07415. Epub 2008 Oct 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18830242" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Eukaryotic Cells/metabolism ; *Evolution, Molecular ; Gene Expression Regulation ; Humans ; MicroRNAs/*genetics ; Phylogeny ; RNA, Small Interfering/*genetics ; Sea Anemones/*genetics ; Sequence Analysis
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 3
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    The widespread impact of mammalian MicroRNAs on mRNA repression and evolution (2005)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2005-11-26
    Description: Thousands of mammalian messenger RNAs are under selective pressure to maintain 7-nucleotide sites matching microRNAs (miRNAs). We found that these conserved targets are often highly expressed at developmental stages before miRNA expression and that their levels tend to fall as the miRNA that targets them begins to accumulate. Nonconserved sites, which outnumber the conserved sites 10 to 1, also mediate repression. As a consequence, genes preferentially expressed at the same time and place as a miRNA have evolved to selectively avoid sites matching the miRNA. This phenomenon of selective avoidance extends to thousands of genes and enables spatial and temporal specificities of miRNAs to be revealed by finding tissues and developmental stages in which messages with corresponding sites are expressed at lower levels.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Farh, Kyle Kai-How -- Grimson, Andrew -- Jan, Calvin -- Lewis, Benjamin P -- Johnston, Wendy K -- Lim, Lee P -- Burge, Christopher B -- Bartel, David P -- New York, N.Y. -- Science. 2005 Dec 16;310(5755):1817-21. Epub 2005 Nov 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology, and Howard Hughes Medical Institute, 9 Cambridge Center, Cambridge, MA 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16308420" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Cell Differentiation ; Conserved Sequence ; *Evolution, Molecular ; Gene Expression Profiling ; *Gene Expression Regulation ; Humans ; Mammals/*genetics ; Mice ; MicroRNAs/*metabolism ; Molecular Sequence Data ; Muscle Fibers, Skeletal/cytology/metabolism ; Organ Specificity ; RNA Stability ; RNA, Messenger/*genetics/metabolism ; Rats ; Species Specificity ; Untranslated Regions ; Zebrafish/genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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