The p97–UBXD8 complex destabilizes mRNA by promoting release of ubiquitinated HuR from mRNP
- Hua-Lin Zhou1,4,5,
- Cuiyu Geng1,
- Guangbin Luo1,2 and
- Hua Lou1,2,3,5
- 1Department of Genetics and Genome Sciences,
- 2Case Comprehensive Cancer Center,
- 3Center for RNA Molecular Biology, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA
Abstract
The assembly and disassembly of ribonucleoproteins (RNPs) are dynamic processes that control every step of RNA metabolism, including mRNA stability. However, our knowledge of how RNP remodeling is achieved is largely limited to RNA helicase functions. Here, we report a previously unknown mechanism that implicates the ATPase p97, a protein-remodeling machine, in the dynamic regulation of mRNP disassembly. We found that p97 and its cofactor, UBXD8, destabilize p21, MKP-1, and SIRT1, three established mRNA targets of the RNA-binding protein HuR, by promoting release of HuR from mRNA. Importantly, ubiquitination of HuR with a short K29 chain serves as the signal for release. When cells are subjected to stress conditions, the steady-state levels of HuR ubiquitination change, suggesting a new mechanism through which HuR mediates the stress response. Our studies reveal a new paradigm in RNA biology: nondegradative ubiquitin signaling-dependent disassembly of mRNP promoted by the p97–UBXD8 complex to control mRNA stability.
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Footnotes
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↵5 Corresponding authors
E-mail hua.lou{at}case.edu
E-mail hlzhou{at}moon.ibp.ac.cn
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Supplemental material is available for this article.
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.215681.113.
- Received February 7, 2013.
- Accepted April 2, 2013.
- Copyright © 2013 by Cold Spring Harbor Laboratory Press