The TRIM-NHL protein NHL-2 is a co-factor in the nuclear and somatic RNAi pathways in C. elegans

  1. Gregory M Davis
  2. Shikui Tu
  3. Joshua W T Anderson
  4. Rhys N Colson
  5. Menachem J Gunzburg
  6. Michelle A Francisco
  7. Debashish Ray
  8. Sean P Shrubsole
  9. Julia A Sobotka
  10. Uri Seroussi
  11. Robert X Lao
  12. Tuhin Maity
  13. Monica Z Wu
  14. Katherine McJunkin
  15. Quaid D Morris
  16. Timothy R Hughes
  17. Jacqueline A Wilce  Is a corresponding author
  18. Julie M Claycomb  Is a corresponding author
  19. Zhiping Weng  Is a corresponding author
  20. Peter R Boag  Is a corresponding author
  1. Federation University, Australia
  2. University of Massachusetts Medical School, United States
  3. Monash University, Australia
  4. University of Toronto, Canada
  5. National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, United States

Abstract

Proper regulation of germline gene expression is essential for fertility and maintaining species integrity. In the C. elegans germline, a diverse repertoire of regulatory pathways promote the expression of endogenous germline genes and limit the expression of deleterious transcripts to maintain genome homeostasis. Here we show that the conserved TRIM-NHL protein, NHL-2, plays an essential role in the C. elegans germline, modulating germline chromatin and meiotic chromosome organization. We uncover a role for NHL-2 as a co-factor in both positively (CSR-1) and negatively (HRDE-1) acting germline 22G-small RNA pathways and the somatic nuclear RNAi pathway. Furthermore, we demonstrate that NHL-2 is a bona fide RNA binding protein and, along with RNA-seq data point to a small RNA independent role for NHL-2 in regulating transcripts at the level of RNA stability. Collectively, our data implicate NHL-2 as an essential hub of gene regulatory activity in both the germline and soma.

Data availability

All small RNA and mRNA Illumina sequencing data have been submitted to the NCBI's Sequence Read Archive (SRA), and are included under project accession number SRP115391.

The following data sets were generated

Article and author information

Author details

  1. Gregory M Davis

    School of Applied and Biomedical Sciences, Federation University, Gippsland, Australia
    Competing interests
    The authors declare that no competing interests exist.
  2. Shikui Tu

    Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Joshua W T Anderson

    Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  4. Rhys N Colson

    Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  5. Menachem J Gunzburg

    Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  6. Michelle A Francisco

    Department of Molecular Genetics, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  7. Debashish Ray

    Department of Molecular Genetics, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  8. Sean P Shrubsole

    Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  9. Julia A Sobotka

    Department of Molecular Genetics, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  10. Uri Seroussi

    Department of Molecular Genetics, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  11. Robert X Lao

    Department of Molecular Genetics, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  12. Tuhin Maity

    Department of Molecular Genetics, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  13. Monica Z Wu

    Department of Molecular Genetics, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  14. Katherine McJunkin

    Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  15. Quaid D Morris

    Department of Molecular Genetics, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  16. Timothy R Hughes

    Department of Molecular Genetics, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  17. Jacqueline A Wilce

    Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Australia
    For correspondence
    jackie.wilce@monash.edu
    Competing interests
    The authors declare that no competing interests exist.
  18. Julie M Claycomb

    Department of Molecular Genetics, University of Toronto, Toronto, Canada
    For correspondence
    julie.claycomb@utoronto.ca
    Competing interests
    The authors declare that no competing interests exist.
  19. Zhiping Weng

    Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, United States
    For correspondence
    zhiping.weng@umassmed.edu
    Competing interests
    The authors declare that no competing interests exist.
  20. Peter R Boag

    Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Monash University, Clayton, Australia
    For correspondence
    peter.boag@monash.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0889-0859

Funding

National Health and Medical Research Council (606575)

  • Peter R Boag

Canada Research Chairs (MOP-274660)

  • Julie M Claycomb

Canadian Institutes of Health Research (MOP-125894)

  • Quaid D Morris
  • Timothy R Hughes

Connaught Fund

  • Julie M Claycomb

National Institutes of Health (HD078253)

  • Zhiping Weng

Canada Research Chairs (CAP- 783 262134)

  • Julie M Claycomb

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

Publication history

  1. Received: January 30, 2018
  2. Accepted: December 20, 2018
  3. Accepted Manuscript published: December 21, 2018 (version 1)
  4. Version of Record published: January 29, 2019 (version 2)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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  1. Gregory M Davis
  2. Shikui Tu
  3. Joshua W T Anderson
  4. Rhys N Colson
  5. Menachem J Gunzburg
  6. Michelle A Francisco
  7. Debashish Ray
  8. Sean P Shrubsole
  9. Julia A Sobotka
  10. Uri Seroussi
  11. Robert X Lao
  12. Tuhin Maity
  13. Monica Z Wu
  14. Katherine McJunkin
  15. Quaid D Morris
  16. Timothy R Hughes
  17. Jacqueline A Wilce
  18. Julie M Claycomb
  19. Zhiping Weng
  20. Peter R Boag
(2018)
The TRIM-NHL protein NHL-2 is a co-factor in the nuclear and somatic RNAi pathways in C. elegans
eLife 7:e35478.
https://doi.org/10.7554/eLife.35478
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