1. Biochemistry and Chemical Biology
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Translation repression via modulation of the cytoplasmic poly(A)-binding protein in the inflammatory response

  1. Xu Zhang
  2. Xiaoli Chen
  3. Qiuying Liu
  4. Shaojie Zhang
  5. Wenqian Hu  Is a corresponding author
  1. Mayo Clinic, United States
  2. University of Central Florida, United States
Research Article
  • Cited 16
  • Views 2,668
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Cite this article as: eLife 2017;6:e27786 doi: 10.7554/eLife.27786

Abstract

Gene expression is precisely regulated during the inflammatory response to control infection and limit the detrimental effects of inflammation. Here, we profiled global mRNA translation dynamics in the mouse primary macrophage-mediated inflammatory response and identified hundreds of differentially translated mRNAs. These mRNAs' 3'UTRs have enriched binding motifs for several RNA-binding proteins, which implies extensive translational regulatory networks. We characterized one such protein, Zfp36, as a translation repressor. Using primary macrophages from a Zfp36-V5 epitope tagged knock-in mouse generated by CRISPR/Cas9-mediated genome editing, we found that the endogenous Zfp36 directly interacts with the cytoplasmic poly(A)-binding protein. Importantly, this interaction is required for the translational repression of Zfp36's target mRNAs in resolving inflammation. Altogether, these results uncovered critical roles of translational regulations in controlling appropriate gene expression during the inflammatory response and revealed a new biologically relevant molecular mechanism of translational repression via modulating the cytoplasmic poly(A)-binding protein.

Data availability

The following data sets were generated
    1. Wenqian Hu
    (2017) Gene Expression Omnibus
    Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE99787).

Article and author information

Author details

  1. Xu Zhang

    Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Xiaoli Chen

    Department of Computer Science, University of Central Florida, Orlando, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Qiuying Liu

    Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Shaojie Zhang

    Department of Computer Science, University of Central Florida, Orlando, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4051-5549
  5. Wenqian Hu

    Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, United States
    For correspondence
    hu.wenqian@mayo.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3577-3604

Funding

Mayo Foundation for Medical Education and Research

  • Wenqian Hu

National Heart, Lung, and Blood Institute (R00HL118157)

  • Wenqian Hu

National Institute of General Medical Sciences (R01GM102515)

  • Shaojie Zhang

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

Ethics

Animal experimentation: All the procedures on the isolation of BMDMs from mice were performed under a protocol (A35015) approved by the Mayo Clinic animal welfare committee.

Reviewing Editor

  1. Torben Heick Jensen, Aarhus University, Denmark

Publication history

  1. Received: April 13, 2017
  2. Accepted: June 20, 2017
  3. Accepted Manuscript published: June 21, 2017 (version 1)
  4. Version of Record published: July 12, 2017 (version 2)

Copyright

© 2017, Zhang 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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