A Tudor domain protein, SIMR-1, promotes siRNA production at piRNA-targeted mRNAs in C. elegans

Abstract

piRNAs play a critical role in the regulation of transposons and other germline genes. In Caenorhabditis elegans, regulation of piRNA target genes is mediated by the mutator complex, which synthesizes high levels of siRNAs through the activity of an RNA-dependent RNA polymerase. However, the steps between mRNA recognition by the piRNA pathway and siRNA amplification by the mutator complex are unknown. Here, we identify the Tudor domain protein, SIMR-1, as acting downstream of piRNA production and upstream of mutator complex-dependent siRNA biogenesis. Interestingly, SIMR-1 also localizes to distinct subcellular foci adjacent to P granules and Mutator foci, two phase-separated condensates that are the sites of piRNA-dependent mRNA recognition and mutator complex-dependent siRNA amplification, respectively. Thus, our data suggests a role for multiple perinuclear condensates in organizing the piRNA pathway and promoting mRNA regulation by the mutator complex.

Data availability

High-throughput sequencing data for RNA-sequencing libraries generated during this study are available through Gene Expression Omnibus (GSE138220 for preliminary simr-1 small RNA, and simr-1 mRNA sequencing data, GSE134573 for mut-16 small RNA and mRNA sequencing data, and GSE145217 for prg-1 and ergo-1 small RNA sequencing data).

The following data sets were generated

Article and author information

Author details

  1. Kevin I Manage

    Biological Sciences, University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1992-0782
  2. Alicia K Rogers

    Biological Sciences, University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Dylan C Wallis

    Biological Sciences, University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Celja J Uebel

    Biological Sciences, University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0362-1238
  5. Dorian C Anderson

    Biological Sciences, University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Dieu An H Nguyen

    Biological Sciences, University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Katerina Arca

    Biological Sciences, University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Kristen C Brown

    Biology, Colorado State University, Fort Collins, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Ricardo J Cordeiro Rodrigues

    Biology of Non-coding RNA Group, Institute of Molecular Biology, Mainz, Germany
    Competing interests
    The authors declare that no competing interests exist.
  10. Bruno F M de Albuquerque

    Biology of Non-coding RNA Group, Institute of Molecular Biology, Mainz, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8483-6822
  11. Rene F Ketting

    Biology of Non-coding RNA Group, Institute of Molecular Biology, Mainz, Germany
    Competing interests
    The authors declare that no competing interests exist.
  12. Taiowa A Montgomery

    Department of Biology, Colorado State University, Fort Collins, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Carolyn Marie Phillips

    Biological Sciences, University of Southern California, Los Angeles, United States
    For correspondence
    cphil@usc.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6228-6468

Funding

National Cancer Institute (K22 CA177897)

  • Carolyn Marie Phillips

National Institute of General Medical Sciences (R35 GM119656)

  • Carolyn Marie Phillips

National Institute of General Medical Sciences (T32 GM118289)

  • Dieu An H Nguyen

National Institute of General Medical Sciences (R35 GM119775)

  • Taiowa A Montgomery

Deutsche Forschungsgemeinschaft (KE1888/1-1)

  • Rene F Ketting

Deutsche Forschungsgemeinschaft (KE1888/1-2)

  • Rene F Ketting

Pew Charitable Trusts (Pew Scholar in the Biomedical Sciences)

  • Carolyn Marie Phillips

National Science Foundation (DGE 1418060)

  • Celja J Uebel

University of Southern California (Dornsife College Chemistry-Biology Interface trainee)

  • Celja J Uebel

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

Reviewing Editor

  1. Oliver Hobert, Howard Hughes Medical Institute, Columbia University, United States

Version history

  1. Received: March 8, 2020
  2. Accepted: April 24, 2020
  3. Accepted Manuscript published: April 27, 2020 (version 1)
  4. Version of Record published: May 28, 2020 (version 2)

Copyright

© 2020, Manage 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. Kevin I Manage
  2. Alicia K Rogers
  3. Dylan C Wallis
  4. Celja J Uebel
  5. Dorian C Anderson
  6. Dieu An H Nguyen
  7. Katerina Arca
  8. Kristen C Brown
  9. Ricardo J Cordeiro Rodrigues
  10. Bruno F M de Albuquerque
  11. Rene F Ketting
  12. Taiowa A Montgomery
  13. Carolyn Marie Phillips
(2020)
A Tudor domain protein, SIMR-1, promotes siRNA production at piRNA-targeted mRNAs in C. elegans
eLife 9:e56731.
https://doi.org/10.7554/eLife.56731

Share this article

https://doi.org/10.7554/eLife.56731

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