Regulatory Expansion in Mammals of Multivalent hnRNP Assemblies that Globally Control Alternative Splicing.

Abstract:

:Alternative splicing (AS) patterns have diverged rapidly during vertebrate evolution, yet the functions of most species- and lineage-specific splicing events are not known. We observe that mammalian-specific AS events are enriched in transcript sequences encoding intrinsically disordered regions (IDRs) of proteins, in particular those containing glycine/tyrosine repeats that mediate formation of higher-order protein assemblies implicated in gene regulation and human disease. These evolutionary changes impact nearly all members of the hnRNP A and D families of RNA binding proteins. Regulation of these events requires formation of unusual, long-range mammalian-specific RNA duplexes. Differential inclusion of the alternative exons controls the formation of tyrosine-dependent multivalent hnRNP assemblies that, in turn, function to globally regulate splicing. Together, our results demonstrate that AS control of IDR-mediated interactions between hnRNPs represents an important and recurring mechanism underlying splicing regulation. Furthermore, this mechanism has expanded the regulatory capacity of mammalian cells.

journal_name

Cell

journal_title

Cell

authors

Gueroussov S,Weatheritt RJ,O'Hanlon D,Lin ZY,Narula A,Gingras AC,Blencowe BJ

doi

10.1016/j.cell.2017.06.037

subject

Has Abstract

pub_date

2017-07-13 00:00:00

pages

324-339.e23

issue

2

eissn

0092-8674

issn

1097-4172

pii

S0092-8674(17)30756-0

journal_volume

170

pub_type

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