Endogenous siRNAs promote proteostasis and longevity in germlineless c .Elegans

Moran Cohen-Berkman; Reut Dudkevich; Shani Ben-Hamo; Alla Fishman; Yehuda Salzberg; Hiba Waldman Ben-Asher; Ayelet T. Lamm; Sivan Henis-Korenblit

doi:10.7554/eLife.50896

Endogenous siRNAs promote proteostasis and longevity in germlineless c .Elegans

Moran Cohen-Berkman, Reut Dudkevich, Shani Ben-Hamo, Alla Fishman, Yehuda Salzberg, Hiba Waldman Ben-Asher, Ayelet T. Lamm, Sivan Henis-Korenblit

The Mina and Everard Goodman Faculty of Life Sciences

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

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 longevitypromoting 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.

Original language	English
Article number	e50896
Journal	eLife
Volume	9
DOIs	https://doi.org/10.7554/eLife.50896
State	Published - 26 Mar 2020

Bibliographical note

Funding Information:
We thank Dr. Jennifer Israel Cohen Benichou for statistical analysis and data presentation and Ms. Yael Laure for English editing. We thank members of the Henis-Korenblit laboratory for helpful discussions. We thank Dr. Shohei Mitani (National Bioresource Project for the nematode, Tokyo Women's Medical University School of Medicine, Japan) and the Caenorhabditis Genetics Center for providing nematode strains. This work was supported by funds from ISF grants no. 1571/15 and 689/19 to S.H.K. and no. 927/18 to ATL, by grant no. 3-12066 from the Israeli Ministry of Science, Technology and Space to S.H.K, and by the Israeli Centers of Research Excellence (I-CORE) program (Center No. 1796/12 to ATL).

Funding Information:
We thank Dr. Jennifer Israel Cohen Benichou for statistical analysis and data 35 presentation and Ms. Yael Laure for English editing. We thank members of 36 the Henis-Korenblit laboratory for helpful discussions. We thank Dr. Shohei 37 Mitani (National Bioresource Project for the nematode, Tokyo Women's 38 Medical University School of Medicine, Japan) and the Caenorhabditis 39 Genetics Center for providing nematode strains. This work was supported by 40 funds from ISF grants no. 1571/15 and 689/19 to S.H.K. and no. 927/18 to 41 ATL, by grant no. 3-12066 from the Israeli Ministry of Science, Technology 42 and Space to S.H.K, and by the Israeli Centers of Research Excellence (I- 43 CORE) program (Center No. 1796/12 to ATL).

Publisher Copyright:
© 2020, eLife Sciences Publications Ltd. All rights reserved.

Keywords

Aging
C.Elegans
Endo-siRNA
Germline
HSF-1
Longevity
Proteostasis

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title = "Endogenous siRNAs promote proteostasis and longevity in germlineless c .Elegans",

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 longevitypromoting 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.",

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AU - Salzberg, Yehuda

AU - Ben-Asher, Hiba Waldman

AU - Lamm, Ayelet T.

AU - Henis-Korenblit, Sivan

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AB - 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 longevitypromoting 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.

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Endogenous siRNAs promote proteostasis and longevity in germlineless c .Elegans

Abstract

Bibliographical note

Keywords

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