Integrative regulatory mapping indicates that the RNA-binding protein HuR couples pre-mRNA processing and mRNA stability.

Abstract:

:RNA-binding proteins coordinate the fates of multiple RNAs, but the principles underlying these global interactions remain poorly understood. We elucidated regulatory mechanisms of the RNA-binding protein HuR, by integrating data from diverse high-throughput targeting technologies, specifically PAR-CLIP, RIP-chip, and whole-transcript expression profiling. The number of binding sites per transcript, degree of HuR association, and degree of HuR-dependent RNA stabilization were positively correlated. Pre-mRNA and mature mRNA containing both intronic and 3' UTR binding sites were more highly stabilized than transcripts with only 3' UTR or only intronic binding sites, suggesting that HuR couples pre-mRNA processing with mature mRNA stability. We also observed HuR-dependent splicing changes and substantial binding of HuR in polypyrimidine tracts of pre-mRNAs. Comparison of the spatial patterns surrounding HuR and miRNA binding sites provided functional evidence for HuR-dependent antagonism of proximal miRNA-mediated repression. We conclude that HuR coordinates gene expression outcomes at multiple interconnected steps of RNA processing.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Mukherjee N,Corcoran DL,Nusbaum JD,Reid DW,Georgiev S,Hafner M,Ascano M Jr,Tuschl T,Ohler U,Keene JD

doi

10.1016/j.molcel.2011.06.007

subject

Has Abstract

pub_date

2011-08-05 00:00:00

pages

327-39

issue

3

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(11)00421-7

journal_volume

43

pub_type

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