1. Biochemistry and Chemical Biology
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MicroRNA-mediated repression of nonsense mRNAs

  1. Ya Zhao
  2. Jimin Lin
  3. Beiying Xu
  4. Sida Hu
  5. Xue Zhang
  6. Ligang Wu  Is a corresponding author
  1. Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, China
Research Article
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Cite this article as: eLife 2014;3:e03032 doi: 10.7554/eLife.03032

Abstract

Numerous studies have established important roles for microRNAs (miRNAs) in regulating gene expression. Here, we report that miRNAs also serve as a surveillance system to repress the expression of nonsense mRNAs that may produce harmful truncated proteins. Upon recognition of the premature termination codon by the translating ribosome, the downstream portion of the coding region of an mRNA is redefined as part of the 3' untranslated region; as a result, the miRNA-responsive elements embedded in this region can be detected by miRNAs, triggering accelerated mRNA deadenylation and translational inhibition. We demonstrate that naturally occurring cancer-causing APC (adenomatous polyposis coli) nonsense mutants which escape nonsense-mediated mRNA decay (NMD) are repressed by miRNA-mediated surveillance. In addition, we show that miRNA-mediated surveillance and exon-exon junction complex-mediated NMD are not mutually exclusive and act additively to enhance the repressive activity. Therefore, we have uncovered a new role for miRNAs in repressing nonsense mutant mRNAs.

Article and author information

Author details

  1. Ya Zhao

    Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Jimin Lin

    Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Beiying Xu

    Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Sida Hu

    Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Xue Zhang

    Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Ligang Wu

    Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    For correspondence
    lgwu@sibcb.ac.cn
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Nick J Proudfoot, University of Oxford, United Kingdom

Publication history

  1. Received: April 15, 2014
  2. Accepted: August 7, 2014
  3. Accepted Manuscript published: August 8, 2014 (version 1)
  4. Version of Record published: September 9, 2014 (version 2)

Copyright

© 2014, Zhao et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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