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 Celljournal_title
Molecular cellauthors
Mukherjee N,Corcoran DL,Nusbaum JD,Reid DW,Georgiev S,Hafner M,Ascano M Jr,Tuschl T,Ohler U,Keene JDdoi
10.1016/j.molcel.2011.06.007subject
Has Abstractpub_date
2011-08-05 00:00:00pages
327-39issue
3eissn
1097-2765issn
1097-4164pii
S1097-2765(11)00421-7journal_volume
43pub_type
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