Kelly, Steven and Georgomanolis, Theodore and Zirkel, Anne and Diermeier, Sarah and O'Reilly, Dawn and Murphy, Shona and Laengst, Gernot and Cook, Peter R. and Papantonis, Argyris (2015) Splicing of many human genes involves sites embedded within introns. NUCLEIC ACIDS RESEARCH, 43 (9). pp. 4721-4732. ISSN 0305-1048, 1362-4962
Full text not available from this repository. (Request a copy)Abstract
The conventional model for splicing involves excision of each intron in one piece; we demonstrate this inaccurately describes splicing in many human genes. First, after switching on transcription of SAMD4A, a gene with a 134 kb-long first intron, splicing joins the 3' end of exon 1 to successive points within intron 1 well before the acceptor site at exon 2 is made. Second, genome-wide analysis shows that >60% of active genes yield products generated by such intermediate intron splicing. These products are present at similar to 15% the levels of primary transcripts, are encoded by conserved sequences similar to those found at canonical acceptors, and marked by distinctive structural and epigenetic features. Finally, using targeted genome editing, we demonstrate that inhibiting the formation of these splicing intermediates affects efficient exon-exon splicing. These findings greatly expand the functional and regulatory complexity of the human transcriptome.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PRE-MESSENGER-RNA; NASCENT TRANSCRIPTION; ELEMENTS; EXON; VERTEBRATE; SEQUENCE; SIGNALS; LENGTH; EXPRESSION; CONSENSUS; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie III > Prof. Dr. Gernot Längst |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 18 Jul 2019 08:45 |
| Last Modified: | 18 Jul 2019 08:45 |
| URI: | https://pred.uni-regensburg.de/id/eprint/5497 |
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