biostudies-otherUnknownDr. Marco GaviraghiAssociazione Italiana per la Ricerca sul Cancro (AIRC)Ministero della Salute (Ministry of Health, Italy)The EMBO Journalhttps://www.ebi.ac.uk/biostudies/studies/S-SCDT-EMBOJ-2018-99179Focal deletions occur frequently in the cancer genome. However, the putative tumor suppressive genes residing within these regions have been difficult to pinpoint. To robustly identify these genes, we implemented a computational approach based on Non-negative Matrix Factorization, NMF and interrogated the TCGA dataset. This analysis revealed a metagene signature including a small subset of genes showing pervasive hemizygous deletions, reduced expression in cancer patient samples and nucleolar function. Amid the genes belonging to this signature, we have identified PNRC1, a nuclear receptor coactivator. We found that PNRC1 interacts with the cytoplasmic DCP1?/DCP2 decapping machinery and hauls it inside the nucleolus. PNRC1-dependent nucleolar translocation of the decapping complex is assocbiostudies-otherDr. Francesca InvernizziDr. Marco GaviraghiDr. Vicent PelechanoDr. Claudia VivoriAngela CattaneoClaudio DoglioniDr. Giovanni TononDavide CittaroDr. Michela FrenquelliDr. Simona SegallaAngela BachiDr. Yerma, P SanchezDr. Benedetta, M SantoliquidofalseTUMOR SUPPRESSOR PNRC1 BLOCKS rRNA MATURATION BY RECRUITING THE DECAPPING COMPLEX TO THE NUCLEOLUSFocal deletions occur frequently in the cancer genome. However, the putative tumor suppressive genes residing within these regions have been difficult to pinpoint. To robustly identify these genes, we implemented a computational approach based on Non-negative Matrix Factorization, NMF and interrogated the TCGA dataset. This analysis revealed a metagene signature including a small subset of genes showing pervasive hemizygous deletions, reduced expression in cancer patient samples and nucleolar function. Amid the genes belonging to this signature, we have identified PNRC1, a nuclear receptor coactivator. We found that PNRC1 interacts with the cytoplasmic DCP1?/DCP2 decapping machinery and hauls it inside the nucleolus. PNRC1-dependent nucleolar translocation of the decapping complex is assoc2019-06-05T23:42:08Z2019-06-05T23:42:08Z2019-06-05T23:42:08ZS-SCDT-EMBOJ-2018-9917910.15252/embj.201899179