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Title: Regulation of alternative splicing in Drosophila by 56 RNA binding proteins

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. In conclusion, 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.
 [1] ;  [2] ;  [2] ;  [2] ;  [2] ;  [3] ;  [3] ;  [3] ;  [3] ;  [3] ;  [2] ;  [4]
  1. Univ. of California, Berkeley, CA (United States); Broad Inst. Cambridge, MA (United States)
  2. Univ. of Connecticut Health Center, Farmington, CT (United States)
  3. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  4. Univ. of California, Berkeley, CA (United States)
Publication Date:
OSTI Identifier:
Grant/Contract Number:
AC02-05CH11231; DRG-2138-12; U01 HG004271
Accepted Manuscript
Journal Name:
Genome Research
Additional Journal Information:
Journal Volume: 25; Journal Issue: 11; Journal ID: ISSN 1088-9051
Cold Spring Harbor Laboratory Press
Research Org:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Org:
Country of Publication:
United States