let-7-repressesed Shc translation delays replicative senescence.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 24165399.
- Also identified by DOI 10.1111/acel.12176 and PMC identifier 3947057.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Cellular Senescence
- MicroRNAs
- Protein Biosynthesis
- Shc Signaling Adaptor Proteins