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TUMOR SUPPRESSOR PNRC1 BLOCKS rRNA MATURATION BY RECRUITING THE DECAPPING COMPLEX TO THE NUCLEOLUS

ABSTRACT: Focal 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 associated with a decrease in the 5'-capped U3 and U8 snoRNA fractions, hampering ribosomal RNA maturation. As a result, PNRC1 ablates the enhanced proliferation triggered by established oncogenes such as RAS and MYC. These observations uncover a previously undescribed mechanism of tumour suppression, whereby the cytoplasmic decapping machinery is hauled within nucleoli, tightly regulating ribosomal RNA maturation.

SUBMITTER: Dr. Marco Gaviraghi

PROVIDER: S-SCDT-EMBOJ-2018-99179 | biostudies-other |

REPOSITORIES: biostudies-other

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