Molecular Cell
Volume 76, Issue 2, 17 October 2019, Pages 329-345
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Review
Alternative Splicing Regulatory Networks: Functions, Mechanisms, and Evolution

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High-throughput sequencing-based methods and their applications in the study of transcriptomes have revolutionized our understanding of alternative splicing. Networks of functionally coordinated and biologically important alternative splicing events continue to be discovered in an ever-increasing diversity of cell types in the context of physiologically normal and disease states. These studies have been complemented by efforts directed at defining sequence codes governing splicing and their cognate trans-acting factors, which have illuminated important combinatorial principles of regulation. Additional studies have revealed critical roles of position-dependent, multivalent protein-RNA interactions that direct splicing outcomes. Investigations of evolutionary changes in RNA binding proteins, splice variants, and associated cis elements have further shed light on the emergence, mechanisms, and functions of splicing networks. Progress in these areas has emphasized the need for a coordinated, community-based effort to systematically address the functions of individual splice variants associated with normal and disease biology.

Keywords

alternative splicing
exon definition
microexon
multivalency
RNP condensate
phase separation
RNA map
cryptic splice site
recursive splicing
evolution

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