microRNA-mediated regulation of microRNA machinery controls cell fate decisions

  1. Qiuying Liu
  2. Mariah K Novak
  3. Rachel M Pepin
  4. Taylor Eich
  5. Wenqian Hu  Is a corresponding author
  1. Mayo Clinic, United States

Abstract

microRNAs associate with Argonaute proteins, forming the microRNA-induced silencing complex (miRISC), to repress target gene expression post-transcriptionally. Although microRNAs are critical regulators in mammalian cell differentiation, our understanding of how microRNA machinery, such as the miRISC, are regulated during development is still limited. We previously showed that repressing the production of one Argonaute protein, Ago2, by Trim71 is important for mouse embryonic stem cells (mESC) self-renewal (Liu et al., 2021). Here we show that among the four Argonaute proteins in mammals, Ago2 is the major developmentally regulated Argonaute protein in mESCs. Moreover, in pluripotency, besides the Trim71-mediated regulation of Ago2 (Liu et al., 2021), Mir182/Mir183 also repress Ago2. Specific inhibition of this microRNA-mediated repression results in stemness defects and accelerated differentiation through the let-7 microRNA pathway. These results reveal a microRNA-mediated regulatory circuit on microRNA machinery that is critical to maintaining pluripotency.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1-5.

The following previously published data sets were used

Article and author information

Author details

  1. Qiuying Liu

    Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1474-4487
  2. Mariah K Novak

    Mayo Clinic, Rochestser, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Rachel M Pepin

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

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

  • Qiuying Liu
  • Mariah K Novak
  • Rachel M Pepin
  • Taylor Eich
  • Wenqian Hu

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

Reviewing Editor

  1. Timothy W Nilsen, Case Western Reserve University, United States

Publication history

  1. Preprint posted: July 21, 2021 (view preprint)
  2. Received: July 21, 2021
  3. Accepted: September 30, 2021
  4. Accepted Manuscript published: October 1, 2021 (version 1)
  5. Version of Record published: October 11, 2021 (version 2)

Copyright

© 2021, Liu 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. Qiuying Liu
  2. Mariah K Novak
  3. Rachel M Pepin
  4. Taylor Eich
  5. Wenqian Hu
(2021)
microRNA-mediated regulation of microRNA machinery controls cell fate decisions
eLife 10:e72289.
https://doi.org/10.7554/eLife.72289

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