Open Accesslet‐7‐repressesed S hc translation delays replicative senescence
Author(s) -
Xu Fang,
Pang Lijun,
Cai Xiaoyu,
Liu Xinwen,
Yuan Shuai,
Fan Xiuqin,
Jiang Bin,
Zhang Xiaowei,
Dou Yali,
Gorospe Myriam,
Wang Wengong
Publication year - 2014
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12176
Subject(s) - biology , translation (biology) , microrna , messenger rna , psychological repression , senescence , signal transducing adaptor protein , regulator , microbiology and biotechnology , genetics , gene expression , gene , phosphorylation
Summary The p66 S hc adaptor protein is an important regulator of lifespan in mammals, but the mechanisms responsible are still unclear. Here, we show that expression of p66 S hc, p52 S hc, and p46 S hc is regulated at the post‐transcriptional level by the micro RNA let‐7a. The levels of let‐7a correlated inversely with the levels of S hc proteins without affecting S hc mRNA levels. We identified ‘seedless’ let‐7a interaction elements in the coding region of S hc mRNA ; mutation of the ‘seedless’ interaction sites abolished the regulation of S hc by let‐7a. Our results further revealed that repression of S hc expression by let‐7a delays senescence of human diploid fibroblasts ( HDF s). In sum, our findings link let‐7a abundance to the expression of p66 S hc, which in turn controls the replicative lifespan of HDF s.