p16 Translation Suppressed by miR-24

Background: Expression of the tumor suppressor p16 increases during aging and replicative senescence. Methodology/Principal Findings: Here, we report that the microRNA miR-24 suppresses p16 expression in human diploid fibroblasts and cervical carcinoma cells. Increased p16 expression with replicative senescence was associated with decreased levels of miR-24, a microRNA that was predicted to associate with the p16 mRNA coding and 39-untranslated regions. Ectopic miR-24 overexpression reduced p16 protein but not p16 mRNA levels. Conversely, introduction of antisense (AS)-miR-24 blocked miR-24 expression and markedly enhanced p16 protein levels, p16 translation, and the production of EGFP-p16 reporter bearing the miR-24 target recognition sites. Conclusions/Significance: Together, our results suggest that miR-24 represses the initiation and elongation phases of p16 translation. Citation: Lal A, Kim HH, Abdelmohsen K, Kuwano Y, Pullmann R, et al. (2008) p16 Translation Suppressed by miR-24. PLoS ONE 3(3): e1864. doi:10.1371/ journal.pone.0001864 Editor: Thomas Preiss, Victor Chang Cardiac Research Institute, Australia Received January 23, 2008; Accepted February 21, 2008; Published March 26, 2008 This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. Funding: National Institute on Aging Intramural Research Program Competing Interests: The authors have declared that no competing interests exist. * E-mail: [email protected] (AL); [email protected] (MG)