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Endogenous siRNAs promote proteostasis and longevity in germline-less Caenorhabditis elegans.

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Cohen-Berkman, Moran 
Dudkevich, Reut 
Ben-Hamo, Shani 
Fishman, Alla 
Salzberg, Yehuda 


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 Caenorhabditis 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.



C. elegans, HSF1, aging, cell biology, developmental biology, endogenous siRNAs, germline, longevity, proteostasis, Animals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Germ Cells, Heat-Shock Response, Longevity, Protein Tyrosine Phosphatases, Proteostasis, RNA, Small Interfering, Transcription Factors

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eLife Sciences Publications, Ltd
Israel Science Foundation (689/19)
Israel Science Foundation (927/18)
Israel Ministry of Science, Technology and Sports (3-12066)
Israeli Centers for Research Excellence (1796/12)