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Tumor suppressor PNRC 1 blocks r RNA maturation by recruiting the decapping complex to the nucleolus
Author(s) -
Gaviraghi Marco,
Vivori Claudia,
Pareja Sanchez Yerma,
Invernizzi Francesca,
Cattaneo Angela,
Santoliquido Benedetta Maria,
Frenquelli Michela,
Segalla Simona,
Bachi Angela,
Doglioni Claudio,
Pelechano Vicent,
Cittaro Davide,
To Giovanni
Publication year - 2018
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201899179
Subject(s) - nucleolus , biology , small nucleolar rna , rna , gene , rna binding protein , ribosomal protein , microbiology and biotechnology , ribosomal rna , genetics , suppressor , cytoplasm , long non coding rna , ribosome
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 PNRC 1, a nuclear receptor coactivator. We found that PNRC 1 interacts with the cytoplasmic DCP 1α/ DCP 2 decapping machinery and hauls it inside the nucleolus. PNRC 1‐dependent nucleolar translocation of the decapping complex is associated with a decrease in the 5′‐capped U3 and U8 sno RNA fractions, hampering ribosomal RNA maturation. As a result, PNRC 1 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.