let‐7‐repressesed Shc translation delays replicative senescence

Aging Cell

Fang Xu¹  Lijun Pang¹  Xiaoyu Cai¹  Xinwen Liu¹  Shuai Yuan¹  Xiuqin Fan¹  Bin Jiang¹  Xiaowei Zhang¹  Yali Dou²  Myriam Gorospe³ 

[1] Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, China;Department of Pathology and Biological Chemistry, University of Michigan, Ann Arbor, MI, USA;Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA

关键词: cellular lifespan;    let‐7a;    p66Shc;    replicative senescence;    translational regulation;   

DOI  :  10.1111/acel.12176

来源: Wiley

【 摘 要 】

Summary

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.

【 授权许可】

CC BY   
© 2013 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.