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Sibley, C.R.* ; Emmett, W.* ; Blazquez, L.* ; Faro, A.* ; Haberman, N.* ; Briese, M.* ; Trabzuni, D.* ; Ryten, M.* ; Weale, M.E.* ; Hardy, J.* ; Modic, M. ; Curk, T.* ; Wilson, S.W.* ; Plagnol, V.* ; Ule, J.*

Recursive splicing in long vertebrate genes.

Nature 521, 371-375 (2015)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
It is generally believed that splicing removes introns as single units from precursor messenger RNA transcripts. However, some long Drosophila melanogaster introns contain a cryptic site, known as a recursive splice site (RS-site), that enables a multi-step process of intron removal termed recursive splicing. The extent to which recursive splicing occurs in other species and its mechanistic basis have not been examined. Here we identify highly conserved RS-sites in genes expressed in the mammalian brain that encode proteins functioning in neuronal development. Moreover, the RS-sites are found in some of the longest introns across vertebrates. We find that vertebrate recursive splicing requires initial definition of an 'RS-exon' that follows the RS-site. The RS-exon is then excluded from the dominant mRNA isoform owing to competition with a reconstituted 5' splice site formed at the RS-site after the first splicing step. Conversely, the RS-exon is included when preceded by cryptic promoters or exons that fail to reconstitute an efficient 5' splice site. Most RS-exons contain a premature stop codon such that their inclusion can decrease mRNA stability. Thus, by establishing a binary splicing switch, RS-sites demarcate different mRNA isoforms emerging from long genes by coupling cryptic elements with inclusion of RS-exons.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Exon Definition; Large Intron; Human Genome; Reveals; Transcription; Expression; Ultrafast; Alignment; Nonsense; Tdp-43
Sprache englisch
Veröffentlichungsjahr 2015
HGF-Berichtsjahr 2015
ISSN (print) / ISBN 0028-0836
e-ISSN 1476-4687
Zeitschrift Nature
Quellenangaben Band: 521, Heft: 7552, Seiten: 371-375 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Stem Cell Research (ISF)
POF Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Forschungsfeld(er) Stem Cell and Neuroscience
PSP-Element(e) G-552400-001
PubMed ID 25970246
DOI 10.1038/nature14466
WOS ID WOS:000354816500060
Scopus ID 84930224948
Erfassungsdatum 2015-05-16
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