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

Journal Article · · Genome Research
 [1];  [2];  [2];  [2];  [2];  [3];  [3];  [3];  [3];  [3];  [2];  [4]
  1. Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cell Biology; Broad Inst. Cambridge, MA (United States); Dana-Farber Cancer Inst., Boston, MA (United States). Dept. of Medical Oncology
  2. Univ. of Connecticut Health Center, Farmington, CT (United States). Dept. of Genetics and Genome Sciences and Inst. for Systems Genomics
  3. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Dept. of Genome Dynamics
  4. Univ. of California, Berkeley, CA (United States). Dept. of Plant and Microbial Biology

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.

Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE; National Science Foundation (NSF); Damon Runyon Cancer Research Foundation, New York City, NY (United States)
Grant/Contract Number:
AC02-05CH11231; DRG-2138-12; U01 HG004271
OSTI ID:
1257380
Alternate ID(s):
OSTI ID: 1474888
Journal Information:
Genome Research, Vol. 25, Issue 11; ISSN 1088-9051
Publisher:
Cold Spring Harbor Laboratory PressCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 57 works
Citation information provided by
Web of Science

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Cited By (21)

Regulatory Mechanisms of Metamorphic Neuronal Remodeling Revealed Through a Genome-Wide Modifier Screen in Drosophila melanogaster journal May 2017
Systematic review regulatory principles of non-coding RNAs in cardiovascular diseases journal August 2017
Modulation of Yorkie activity by alternative splicing is required for developmental stability journal December 2020
Transcriptome 3′end organization by PCF11 links alternative polyadenylation to formation and neuronal differentiation of neuroblastoma journal December 2018
sCLIP—an integrated platform to study RNA–protein interactomes in biomedical research: identification of CSTF2tau in alternative processing of small nuclear RNAs journal February 2017
The RNA helicase UPF1 associates with mRNAs co-transcriptionally and is required for the release of mRNAs from gene loci journal March 2019
The transcriptome-wide landscape and modalities of EJC binding in adult Drosophila journal November 2018
The transcriptome-wide landscape and modalities of EJC binding in adult Drosophila. text January 2020
The Fragile X Protein and Genome Function journal May 2018
SURF: integrative analysis of a compendium of RNA-seq and CLIP-seq datasets highlights complex governing of alternative transcriptional regulation by RNA-binding proteins posted_content May 2020
Extensive Differential Splicing Underlies Phenotypically Plastic Aphid Morphs journal May 2018
HITS-CLIP reveals sex-differential RNA binding and alterative splicing regulation of SRm160 in Drosophila journal May 2018
Quantifying post-transcriptional regulation in the development of Drosophila melanogaster journal November 2018
SURF: integrative analysis of a compendium of RNA-seq and CLIP-seq datasets highlights complex governing of alternative transcriptional regulation by RNA-binding proteins journal June 2020
Proper splicing contributes to visual function in the aging Drosophila eye journal July 2018
Spliceosome factors target timeless (tim) mRNA to control clock protein accumulation and circadian behavior in Drosophila journal December 2018
The SR protein B52/SRp55 regulates splicing of the period thermosensitive intron and mid-day siesta in Drosophila journal January 2018
Ecdysone signaling promotes expression of multifunctional RNA binding proteins essential for ovarian germline stem cell self-renewal in Drosophila posted_content February 2019
Pervasive Strong Selection at the Level of Codon Usage Bias in Drosophila melanogaster journal December 2019
The Interplay of Temperature and Genotype on Patterns of Alternative Splicing in Drosophila melanogaster journal July 2016
The Ski2-family helicase Obelus regulates Crumbs alternative splicing and cell polarity journal December 2015

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