Getting Involved Locally

Abstract

Molecular Biology MicroRNAs (miRNAs) are small RNAs of around 22 nucleotides that bind to protein-coding messenger RNAs (mRNAs). They regulate function in diverse cellular processes, particularly during development and also in cancer. Understanding how miRNAs themselves are regulated is an emerging area of interest. The cyclin-dependent kinase inhibitor p27 negatively regulates the G1 to S phase transition of the cell cycle. Translation of p27 mRNA is inhibited in many cancer cell types by two miRNAs, miR-221 and miR-222. However, p27 accumulates in nondividing (quiescent) cells, despite the presence of high levels of miR-221 and miR-222, suggesting an additional level of regulation. Kedde et al. have discovered that the ability of these miRNAs to inhibit p27 is regulated by another RNA binding protein, Pumilio-1. The binding site of Pumilio-1 in the 3' untranslated region of p27 is located close to the binding sites for miR-221 and miR-222. The authors found that Pumilio-1 binding could reconfigure the local RNA structure, thereby granting the two miRNAs access. They propose that entry into the cell cycle of quiescent cells involves phosphorylation of Pumilio 1, which stimulates its binding to p27 mRNA, thereby exposing the nearby miRNA binding sites. These results suggest that specific binding proteins can structurally remodel RNAs, like they do chromatin, in order to regulate function. Nat. Cell Biol. 12 , 10.1038/ncb2105 (2010).