Ricerc@Sapienza

MiRNAs are small non-coding RNA molecules that regulate gene expression at the post-transcriptional level. These guide RNAs direct the RNA-induced silencing complex (RISC) to complementary mRNAs that are targets for RISC-mediated gene silencing. Binding of RISC to a partially complementary mRNA results in silencing through inhibition of translation. Subsequently, both Dicer and the Argonaute protein family were discovered to have expanded roles in gene regulation including their relocalization to the nucleus where they participate in transcription, alternative splicing and even DNA repair.
To date, although many data have highlighted the role played by miRNAs in controlling gene expression, the mechanisms regulating RISC protein components expression are largely unknown. Recently, we observed a modified expression of Ago2 mRNA and protein in both WI38 fibroblasts and MCF-7 committed to senescence. Specifically, in senescent cells we obtained decreased levels of Ago2 mRNA compared to the young biological sample. In contrast, the same biological samples showed unchanged levels of the Ago2 protein. Moreover, the altered Ago2 expression was accompanied to its cellular redistribution with an enrichment to the nucleus. Overall, this first set of results leads us to investigate the molecular mechanisms controlling the expression and the post-translational modifications of Ago2 inducing the cellular relocalization of the protein in cells committed to senescence.