Endogenous siRNAs promote proteostasis and longevity in germline less C. elegans

  1. Moran Cohen-Berkman
  2. Reut Dudkevich
  3. Shani Ben-Hamo
  4. Alla Fishman
  5. Yehuda Salzberg
  6. Hiba Waldman Ben-Asher
  7. Ayelet T Lamm
  8. Sivan Henis-Korenblit  Is a corresponding author
  1. Bar-Ilan University, Israel
  2. Technion - Israel Institute of Technology, Israel
  3. Weizmann Institute of Science, Israel

Abstract

How lifespan and the rate of aging are set is a key problem in biology. Small RNAs are conserved molecules that impact diverse biological processes through the control of gene expression. However, in contrast to miRNAs, the role of endo-siRNAs in aging remains unexplored. Here, by combining deep sequencing and genomic and genetic approaches in C. elegans, we reveal an unprecedented role for endo-siRNA molecules in the maintenance of proteostasis and lifespan extension in germline-less animals. Furthermore, we identify an endo-siRNA-regulated tyrosine phosphatase, which limits the longevity of germline-less animals by restricting the activity of the heat shock transcription factor HSF-1. Altogether, our findings point to endo-siRNAs as a link between germline removal and the HSF-1 proteostasis and longevity-promoting somatic pathway. This establishes a role for endo siRNAs in the aging process and identifies downstream genes and physiological processes that are regulated by the endo siRNAs to affect longevity.

Data availability

Raw and processed high-throughput sequencing data and microarray data generated and/or analyzed during this study were deposited under the Gene Expression Omnibus, with accession number GSE122457 and GSE128935.All other data generated or analysed during this study are included in the manuscript and supporting files.

The following data sets were generated

Article and author information

Author details

  1. Moran Cohen-Berkman

    Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel
    Competing interests
    The authors declare that no competing interests exist.
  2. Reut Dudkevich

    The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel
    Competing interests
    The authors declare that no competing interests exist.
  3. Shani Ben-Hamo

    Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel
    Competing interests
    The authors declare that no competing interests exist.
  4. Alla Fishman

    Faculty of Biology, Technion - Israel Institute of Technology, Haifa, Israel
    Competing interests
    The authors declare that no competing interests exist.
  5. Yehuda Salzberg

    Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
  6. Hiba Waldman Ben-Asher

    Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel
    Competing interests
    The authors declare that no competing interests exist.
  7. Ayelet T Lamm

    Faculty of Biology, Technion - Israel Institute of Technology, Haifa, Israel
    Competing interests
    The authors declare that no competing interests exist.
  8. Sivan Henis-Korenblit

    The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel
    For correspondence
    sivan.korenblit@biu.ac.il
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8023-6336

Funding

Israel Science Foundation (689/19)

  • Sivan Henis-Korenblit

Israel Science Foundation (927/18)

  • Ayelet T Lamm

Israel Ministry of Science, Technology and Space (3-12066)

  • Sivan Henis-Korenblit

Israeli Centers for Research Excellence (1796/12)

  • Ayelet T Lamm

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

Reviewing Editor

  1. Matt Kaeberlein, University of Washington, United States

Version history

  1. Received: August 6, 2019
  2. Accepted: March 26, 2020
  3. Accepted Manuscript published: March 26, 2020 (version 1)
  4. Version of Record published: April 6, 2020 (version 2)

Copyright

© 2020, Cohen-Berkman 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. Moran Cohen-Berkman
  2. Reut Dudkevich
  3. Shani Ben-Hamo
  4. Alla Fishman
  5. Yehuda Salzberg
  6. Hiba Waldman Ben-Asher
  7. Ayelet T Lamm
  8. Sivan Henis-Korenblit
(2020)
Endogenous siRNAs promote proteostasis and longevity in germline less C. elegans
eLife 9:e50896.
https://doi.org/10.7554/eLife.50896

Share this article

https://doi.org/10.7554/eLife.50896

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