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Let-7-repressesed Shc translation delays replicative senescence.

ABSTRACT: The p66Shc adaptor protein is an important regulator of lifespan in mammals, but the mechanisms responsible are still unclear. Here, we show that expression of p66Shc, p52Shc, and p46Shc is regulated at the post-transcriptional level by the microRNA let-7a. The levels of let-7a correlated inversely with the levels of Shc proteins without affecting Shc mRNA levels. We identified 'seedless' let-7a interaction elements in the coding region of Shc mRNA; mutation of the 'seedless' interaction sites abolished the regulation of Shc by let-7a. Our results further revealed that repression of Shc expression by let-7a delays senescence of human diploid fibroblasts (HDFs). In sum, our findings link let-7a abundance to the expression of p66Shc, which in turn controls the replicative lifespan of HDFs.

SUBMITTER: Xu F

PROVIDER: S-EPMC3947057 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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let-7-repressesed Shc translation delays replicative senescence.

Xu Fang F Pang Lijun L Cai Xiaoyu X Liu Xinwen X Yuan Shuai S Fan Xiuqin X Jiang Bin B Zhang Xiaowei X Dou Yali Y Gorospe Myriam M Wang Wengong W

Aging cell 20131125 1

The p66Shc adaptor protein is an important regulator of lifespan in mammals, but the mechanisms responsible are still unclear. Here, we show that expression of p66Shc, p52Shc, and p46Shc is regulated at the post-transcriptional level by the microRNA let-7a. The levels of let-7a correlated inversely with the levels of Shc proteins without affecting Shc mRNA levels. We identified 'seedless' let-7a interaction elements in the coding region of Shc mRNA; mutation of the 'seedless' interaction sites a ...[more]

PMID: 24165399

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