Decoupling the impact of microRNAs on translational repression versus RNA degradation in embryonic stem cells

  1. Jacob W Freimer
  2. TJ Hu
  3. Robert Blelloch  Is a corresponding author
  1. University of California, San Francisco, United States

Abstract

Translation and mRNA degradation are intimately connected, yet the mechanisms that link them are not fully understood. Here we studied these mechanisms in embryonic stem cells (ESCs). Transcripts showed a wide range of stabilities, which correlated with their relative translation levels and that did not change during early ESC differentiation. The protein DHH1 links translation to mRNA stability in yeast; however, loss of the mammalian homolog, DDX6, in ESCs did not disrupt the correlation across transcripts. Instead, the loss of DDX6 led to upregulated translation of microRNA targets, without concurrent changes in mRNA stability. The Ddx6 knockout cells were phenotypically and molecularly similar to cells lacking all microRNAs (Dgcr8 knockout ESCs). These data show that the loss of DDX6 can separate the two canonical functions of microRNAs: translational repression and transcript destabilization. Furthermore, these data uncover a central role for translational repression independent of transcript destabilization in defining the downstream consequences of microRNA loss.

Data availability

Sequencing data have been deposited in GEO under accession codes GSE112767.

The following data sets were generated

Article and author information

Author details

  1. Jacob W Freimer

    Department of Urology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9239-2272
  2. TJ Hu

    Department of Urology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Robert Blelloch

    Department of Urology, University of California, San Francisco, San Francisco, United States
    For correspondence
    robert.blelloch@ucsf.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1975-0798

Funding

National Institute of General Medical Sciences (GM101180)

  • Robert Blelloch

National Institute of General Medical Sciences (GM122439)

  • Robert Blelloch

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Nahum Sonenberg, McGill University, Canada

Publication history

  1. Received: May 2, 2018
  2. Accepted: July 24, 2018
  3. Accepted Manuscript published: July 25, 2018 (version 1)
  4. Version of Record published: August 10, 2018 (version 2)

Copyright

© 2018, Freimer 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. Jacob W Freimer
  2. TJ Hu
  3. Robert Blelloch
(2018)
Decoupling the impact of microRNAs on translational repression versus RNA degradation in embryonic stem cells
eLife 7:e38014.
https://doi.org/10.7554/eLife.38014

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