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Protein Modularity of Alternatively Spliced Exons Is Associated with Tissue-Specific Regulation of Alternative Splicing

Journal Article · · PLoS Genetics
 [1];  [2]
  1. Univ. of California, Los Angeles, CA (United States). Dept. of Chemsitry and Biochemistry. Molecular Biology Inst. Inst. for Genomics and Proteomics; DOE/OSTI
  2. Univ. of California, Los Angeles, CA (United States). Dept. of Chemsitry and Biochemistry. Molecular Biology Inst. Inst. for Genomics and Proteomics
Recent comparative genomic analysis of alternative splicing has shown that protein modularity is an important criterion for functional alternative splicing events. Exons that are alternatively spliced in multiple organisms are much more likely to be an exact multiple of 3 nt in length, representing a class of ‘‘modular’’ exons that can be inserted or removed from the transcripts without affecting the rest of the protein. To understand the precise roles of these modular exons, in this paper we have analyzed microarray data for 3,126 alternatively spliced exons across ten mouse tissues generated by Pan and coworkers. We show that modular exons are strongly associated with tissue-specific regulation of alternative splicing. Exons that are alternatively spliced at uniformly high transcript inclusion levels or uniformly low levels show no preference for protein modularity. In contrast, alternatively spliced exons with dramatic changes of inclusion levels across mouse tissues (referred to as ‘‘tissue-switched’’ exons) are both strikingly biased to be modular and are strongly conserved between human and mouse. The analysis of different subsets of tissue switched exons shows that the increased protein modularity cannot be explained by the overall exon inclusion level, but is specifically associated with tissue-switched alternative splicing.
Research Organization:
Univ. of California, Los Angeles, CA (United States)
Sponsoring Organization:
National Institutes of Health (NIH); USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
Grant/Contract Number:
FC02-02ER63421
OSTI ID:
1627262
Journal Information:
PLoS Genetics, Journal Name: PLoS Genetics Journal Issue: 3 Vol. 1; ISSN 1553-7404
Publisher:
Public Library of ScienceCopyright Statement
Country of Publication:
United States
Language:
English

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Cited By (21)

Alternative splicing regulation at tandem 3' splice sites journal January 2006
The ASAP II database: analysis and comparative genomics of alternative splicing in 15 animal species journal January 2007
Splicing factor and exon profiling across human tissues journal January 2010
High resolution analysis of the human transcriptome: detection of extensive alternative splicing independent of transcriptional activity journal October 2009
Functional importance of different patterns of correlation between adjacent cassette exons in human and mouse journal April 2008
Identification and characterization of bovine regulator of telomere length elongation helicase gene (RTEL): molecular cloning, expression distribution, splice variants and DNA methylation profile journal March 2007
Defining structural and evolutionary modules in proteins: a community detection approach to explore sub-domain architecture journal January 2013
Where Do Introns Come From? journal November 2008
Predicting Functional Alternative Splicing by Measuring RNA Selection Pressure from Multigenome Alignments journal December 2009
Evolution of Nova-dependent splicing regulation in the brain journal January 2005
The identification of switch-like alternative splicing exons among multiple samples with RNA-Seq data journal May 2017
Insights into the association of Gla-rich protein and osteoarthritis, novel splice variants and γ-carboxylation status journal May 2014
Alternative isoform regulation in human tissue transcriptomes journal November 2008
MBNL1 and RBFOX2 cooperate to establish a splicing programme involved in pluripotent stem cell differentiation journal September 2013
RNA splicing factors as oncoproteins and tumour suppressors journal June 2016
The ribosome-engaged landscape of alternative splicing journal November 2016
Large-scale analysis of exonized mammalian-wide interspersed repeats in primate genomes journal March 2009
MATS: a Bayesian framework for flexible detection of differential alternative splicing from RNA-Seq data journal January 2012
Lineage-specific splicing of a brain-enriched alternative exon promotes glioblastoma progression journal May 2014
Correspondence of D. melanogaster and C. elegans developmental stages revealed by alternative splicing characteristics of conserved exons journal March 2017
Inflammation-Induced Alternative Pre-mRNA Splicing in Mouse Alveolar Macrophages journal February 2020

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