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Regulation of alternative splicing in Drosophila by 56 RNA binding proteins.

Authors
  • Angela Brooks
  • Mo, Duff
  • G, May
  • L, Yang
  • M, Bolisetty
  • J, Landolin
  • K, Wan
  • J, Sandler
  • Bw, Booth
  • Se, Celniker
  • Br, Graveley
  • Se, Brenner
Type
Published Article
Journal
Genome Research
Publisher
Cold Spring Harbor Laboratory
Volume
25
Issue
11
Pages
1771–1780
Identifiers
DOI: 10.1101/gr.192518.115
Source
UCSC Cancer biomedical-ucsc
License
Unknown

Abstract

Alternative splicing is regulated by RNA binding proteins (RBPs) that recognize pre-mRNA sequence elements and activate or repress adjacent exons. Here, we used RNA interference and RNA-seq to identify splicing events regulated by 56 Drosophila proteins, some previously unknown to regulate splicing. Nearly all proteins affected alternative first exons, suggesting that RBPs play important roles in first exon choice. Half of the splicing events were regulated by multiple proteins, demonstrating extensive combinatorial regulation. We observed that SR and hnRNP proteins tend to act coordinately with each other, not antagonistically. We also identified a cross-regulatory network where splicing regulators affected the splicing of pre-mRNAs encoding other splicing regulators. This large-scale study substantially enhances our understanding of recent models of splicing regulation and provides a resource of thousands of exons that are regulated by 56 diverse RBPs.

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