Cotranslational microRNA mediated messenger RNA destabilization

  1. Trinh To Tat
  2. Patricia A Maroney
  3. Sangpen Chamnongpol
  4. Jeff Coller
  5. Timothy W Nilsen  Is a corresponding author
  1. Case Western Reserve University, United States
  2. Affymetrix, Inc., United States

Abstract

MicroRNAs are small (22 nucleotide) regulatory molecules that play important roles in a wide variety of biological processes. These RNAs, which bind to targeted mRNAs via limited base pairing interactions, act to reduce protein production from those mRNAs. Considerable evidence indicates that miRNAs destabilize targeted mRNAs by recruiting enzymes that function in normal mRNA decay and mRNA degradation is widely thought to occur when mRNAs are in a ribosome free state. Nevertheless, when examined, miRNA targeted mRNAs are invariably found to be polysome associated; observations that appear to be at face value incompatible with a simple decay model. Here, we provide evidence that turnover of miRNA-targeted mRNAs occurs while they are being translated. Cotranslational mRNA degradation is initiated by decapping and proceeds 5' to 3' behind the last translating ribosome. These results provide an explanation for a long standing mystery in the miRNA field.

Article and author information

Author details

  1. Trinh To Tat

    Center for RNA Molecular Biology, Case Western Reserve University, Cleveland, United States
    Competing interests
    No competing interests declared.
  2. Patricia A Maroney

    Center for RNA Molecular Biology, Case Western Reserve University, Cleveland, United States
    Competing interests
    No competing interests declared.
  3. Sangpen Chamnongpol

    Affymetrix, Inc., Cleveland, United States
    Competing interests
    No competing interests declared.
  4. Jeff Coller

    Center for RNA Molecular Biology, Case Western Reserve University, Cleveland, United States
    Competing interests
    No competing interests declared.
  5. Timothy W Nilsen

    Center for RNA Molecular Biology, Case Western Reserve University, Cleveland, United States
    For correspondence
    twn@case.edu
    Competing interests
    Timothy W Nilsen, Reviewing editor, eLife.

Reviewing Editor

  1. Douglas L Black, University of California, Los Angeles, United States

Publication history

  1. Received: November 7, 2015
  2. Accepted: April 7, 2016
  3. Accepted Manuscript published: April 8, 2016 (version 1)
  4. Version of Record published: May 6, 2016 (version 2)

Copyright

© 2016, Tat 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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  1. Trinh To Tat
  2. Patricia A Maroney
  3. Sangpen Chamnongpol
  4. Jeff Coller
  5. Timothy W Nilsen
(2016)
Cotranslational microRNA mediated messenger RNA destabilization
eLife 5:e12880.
https://doi.org/10.7554/eLife.12880
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