Tumor suppressor PNRC1 blocks rRNA maturation by recruiting the decapping complex to the nucleolus.
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Gaviraghi M, Vivori C, Pareja Sanchez Y, Invernizzi F, Cattaneo A, Santoliquido BM, Frenquelli M, Segalla S, Bachi A, Doglioni C, Pelechano V, Cittaro D, Tonon G
EMBO J. 37 (23) - [2018-12-03; online 2018-10-29]
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 DCP1α/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 tumor suppression, whereby the cytoplasmic decapping machinery is hauled within nucleoli, tightly regulating ribosomal RNA maturation.
PubMed 30373810
DOI 10.15252/embj.201899179
Crossref 10.15252/embj.201899179
pii: embj.201899179
pmc: PMC6276881