Thu, 21 Aug 2008 00:48:33 BST CiteULike: maralena's e2f http://www.citeulike.org/user/maralena/tag/e2f CiteULike.org en-gb Copyright © 2004-2008 citeulike.org http://www.citeulike.org/user/maralena/article/974000 <i>J Biol Chem (29 November 2006)</i><br /><br />MicroRNAs (miRNAs) are a class of non-coding RNAs that post-transcriptionally regulate gene expression via the RNA interference (RNAi) pathway. In addition to roles in normal development, miRNAs have recently been implicated in a range of human diseases, including cancer. We recently demonstrated that a polycistronic cluster of miRNAs, miR-17~92, is oncogenic in a mouse model for Burkitt's lymphoma. This is due, in part, to a reduced apoptotic program. In an effort to understand the regulation of miR-17~92, we have studied the promoter structure of this miRNA cluster. The primary transcript initiates from a consensus initiator sequence downstream of a nonconsensus TATA box. The core promoter region contains two functional E2F transcription factor binding sites. Chromatin immunoprecipitation demonstrates that E2F3 is the primary E2F family member that occupies the promoter. These data place miR-17~92 in a regulatory loop between E2F3 and the miR-17 target E2F1. We propose a model whereby miR-17~92 promotes cell proliferation by shifting the E2F transcriptional balance away from the pro-apoptotic E2F1 and towards the proliferative E2F3 transcriptional network. Direct regulation of an oncogenic microRNA cluster by E2F transcription factors. Keith Woods J Michael Thomson Scott M Hammond doi:10.1074/jbc.C600252200 J Biol Chem (29 November 2006) 2006-12-05T00:28:05-00:00 2006 J Biol Chem 0021-9258 e2f microrna mir-17-92 tf http://www.citeulike.org/user/maralena/article/972914 <i>J Biol Chem (29 November 2006)</i><br /><br />The E2F family of transcription factors is essential in the regulation of the cell cycle and apoptosis. While the activity of E2F1-3 is tightly controlled by the Retinoblastoma (Rb) family of proteins, the expression of these factors is also regulated at the level of transcription, post-translational modifications and protein stability. Recently, a new level of regulation of E2Fs has been identified, where microRNAs (miRNAs) from the mir-17-92 cluster influence the translation of the E2F1 mRNA. We now report that miR-20a, a member of the mir-17-92 cluster, modulates the translation of the E2F2 and E2F3 mRNAs via binding sites in their 3'UTR. We also found that the endogenous E2F1, E2F2 and E2F3 directly bind the promoter of the mir-17-92 cluster activating its transcription, suggesting an auto-regulatory feed-back loop between E2F factors and miRNAs from the mir-17-92 cluster. Our data also point toward an anti-apoptotic role for miR-20a, since overexpression of this miRNA decreased apoptosis in a prostate cancer cell line, while inhibition of miR-20a by an antisense oligonucleotide resulted in increased cell death after doxorubicin treatment. This anti-apoptotic role of miR-20a may explain some of the oncogenic capacities of the mir-17-92 cluster. Altogether, these results suggest that the auto-regulation between E2F1-3 and miR-20a is important for preventing an abnormal accumulation of E2F1-3 and may play a role in the regulation of cellular proliferation and apoptosis. An E2F/miR-20a auto-regulatory feed-back loop. Yannick Sylvestre Vincent De Guire Emmanuelle Querido Utpal K Mukhopadhyay Véronique Bourdeau François Major Gerardo Ferbeyre Pascal Chartrand doi:10.1074/jbc.M608939200 J Biol Chem (29 November 2006) 2006-12-04T08:53:21-00:00 2006 J Biol Chem 0021-9258 e2f feedback microrna mir-20a