The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
Faculty of Biology, Technion-Israel Institute of Technology, Technion City, Haifa, Israel.
Elife. 2020 Mar 26;9:e50896. doi: 10.7554/eLife.50896.
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 , 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.
寿命和衰老速度是如何设定的是生物学中的一个关键问题。小 RNA 是保守的分子,通过控制基因表达来影响多种生物过程。然而,与 miRNAs 不同,endo-siRNAs 在衰老中的作用仍未被探索。在这里,我们通过结合深度测序以及基因组和遗传方法,揭示了 endo-siRNA 分子在维持生殖系缺失动物的蛋白质平衡和延长寿命方面的前所未有的作用。此外,我们鉴定了一种受 endo-siRNA 调控的酪氨酸磷酸酶,它通过限制热休克转录因子 HSF-1 的活性来限制生殖系缺失动物的寿命。总之,我们的发现表明 endo-siRNAs 是生殖系去除与 HSF-1 蛋白质平衡和促进长寿的体体面途径之间的联系。这确立了 endo-siRNAs 在衰老过程中的作用,并确定了受 endo-siRNAs 调控以影响寿命的下游基因和生理过程。