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

Item Type:Article
Title:Integrative regulatory mapping indicates that the RNA-binding protein HuR couples pre-mRNA processing and mRNA stability
Creators Name:Mukherjee, N. and Corcoran, D.L. and Nusbaum, J.D. and Reid, D.W. and Georgiev, S. and Hafner, M. and Ascano, M. and Tuschl, T. and Ohler, U. and Keene, J.D.
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.
Keywords:Amino Acid Motifs, Binding Sites, Computational Biology, Gene Expression Regulation, HEK293 Cells, Messenger RNA, MicroRNAs, Post-Transcriptional RNA Processing, RNA-Binding Proteins, RNA Precursors, RNA Stability, Software, Surface Antigens
Source:Molecular Cell
Publisher:Cell Press
Page Range:327-339
Date:5 August 2011
Official Publication:https://doi.org/10.1016/j.molcel.2011.06.007
PubMed:View item in PubMed

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