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Nucleic Acids Res. 2015 May 19;43(9):4721-32. doi: 10.1093/nar/gkv386. Epub 2015 Apr 20.

Splicing of many human genes involves sites embedded within introns.

Author information

1
Department of Plant Sciences, University of Oxford, Oxford OX1 3RB, United Kingdom.
2
Centre for Molecular Medicine, University of Cologne, Cologne D-50931, Germany.
3
Institut für Biochemie III, University of Regensburg, Regensburg D-93053, Germany.
4
Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom.
5
Centre for Molecular Medicine, University of Cologne, Cologne D-50931, Germany argyris.papantonis@uni-koeln.de.

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 ∼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.

PMID:
25897131
PMCID:
PMC4482092
DOI:
10.1093/nar/gkv386
[Indexed for MEDLINE]
Free PMC Article

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