Endogenous siRNAs promote proteostasis and longevity in germline less 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 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.
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endo-siRNAs repress a neddylation inhibitor to promote longevity and proteostasisNCBI Gene Expression Omnibus, GSE128935.
Article and author information
Author details
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.
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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