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

Publication ,  Journal Article
Mukherjee, N; Corcoran, DL; Nusbaum, JD; Reid, DW; Georgiev, S; Hafner, M; Ascano, M; Tuschl, T; Ohler, U; Keene, JD
Published in: Mol Cell
August 5, 2011

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.

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Published In

Mol Cell

DOI

EISSN

1097-4164

Publication Date

August 5, 2011

Volume

43

Issue

3

Start / End Page

327 / 339

Location

United States

Related Subject Headings

  • Software
  • RNA-Binding Proteins
  • RNA, Messenger
  • RNA Stability
  • RNA Processing, Post-Transcriptional
  • RNA Precursors
  • MicroRNAs
  • Humans
  • HEK293 Cells
  • Gene Expression Regulation
 

Citation

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Mukherjee, N., Corcoran, D. L., Nusbaum, J. D., Reid, D. W., Georgiev, S., Hafner, M., … Keene, J. D. (2011). Integrative regulatory mapping indicates that the RNA-binding protein HuR couples pre-mRNA processing and mRNA stability. Mol Cell, 43(3), 327–339. https://doi.org/10.1016/j.molcel.2011.06.007
Mukherjee, Neelanjan, David L. Corcoran, Jeffrey D. Nusbaum, David W. Reid, Stoyan Georgiev, Markus Hafner, Manuel Ascano, Thomas Tuschl, Uwe Ohler, and Jack D. Keene. “Integrative regulatory mapping indicates that the RNA-binding protein HuR couples pre-mRNA processing and mRNA stability.Mol Cell 43, no. 3 (August 5, 2011): 327–39. https://doi.org/10.1016/j.molcel.2011.06.007.
Mukherjee N, Corcoran DL, Nusbaum JD, Reid DW, Georgiev S, Hafner M, et al. Integrative regulatory mapping indicates that the RNA-binding protein HuR couples pre-mRNA processing and mRNA stability. Mol Cell. 2011 Aug 5;43(3):327–39.
Mukherjee, Neelanjan, et al. “Integrative regulatory mapping indicates that the RNA-binding protein HuR couples pre-mRNA processing and mRNA stability.Mol Cell, vol. 43, no. 3, Aug. 2011, pp. 327–39. Pubmed, doi:10.1016/j.molcel.2011.06.007.
Mukherjee N, Corcoran DL, Nusbaum JD, Reid DW, Georgiev S, Hafner M, Ascano M, Tuschl T, Ohler U, Keene JD. Integrative regulatory mapping indicates that the RNA-binding protein HuR couples pre-mRNA processing and mRNA stability. Mol Cell. 2011 Aug 5;43(3):327–339.
Journal cover image

Published In

Mol Cell

DOI

EISSN

1097-4164

Publication Date

August 5, 2011

Volume

43

Issue

3

Start / End Page

327 / 339

Location

United States

Related Subject Headings

  • Software
  • RNA-Binding Proteins
  • RNA, Messenger
  • RNA Stability
  • RNA Processing, Post-Transcriptional
  • RNA Precursors
  • MicroRNAs
  • Humans
  • HEK293 Cells
  • Gene Expression Regulation