Abstract
| Original language | English |
|---|---|
| Article number | e99179 |
| Journal | EMBO Journal |
| Volume | 37 |
| Issue number | 23 |
| Publication status | Published - 2018 |
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Tumor suppressor PNRC1 blocks rRNA maturation by recruiting the decapping complex to the nucleolus. / 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.
In: EMBO Journal, Vol. 37, No. 23, e99179, 2018.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Tumor suppressor PNRC1 blocks rRNA maturation by recruiting the decapping complex to the nucleolus
AU - Gaviraghi, M
AU - Vivori, C
AU - Pareja Sanchez, Y
AU - Invernizzi, F
AU - Cattaneo, A
AU - Santoliquido, BM
AU - Frenquelli, M
AU - Segalla, S
AU - Bachi, A
AU - Doglioni, C
AU - Pelechano, V
AU - Cittaro, D
AU - Tonon, G
PY - 2018
Y1 - 2018
N2 - 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. © 2018 The Authors
AB - 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. © 2018 The Authors
M3 - Article
VL - 37
JO - EMBO Journal
JF - EMBO Journal
SN - 0261-4189
IS - 23
M1 - e99179
ER -