Tumor suppressor PNRC1 blocks rRNA maturation by recruiting the decapping complex to the nucleolus

EMBO J. 2018 Dec 3;37(23):e99179. doi: 10.15252/embj.201899179. Epub 2018 Oct 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.

Keywords: RNA decapping; cancer; nucleolus; rRNA processing; tumor suppressor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Cell Nucleolus / genetics
  • Cell Nucleolus / metabolism*
  • Cell Nucleolus / pathology
  • Cell Proliferation*
  • Databases, Nucleic Acid
  • Endoribonucleases / genetics
  • Endoribonucleases / metabolism
  • HeLa Cells
  • Humans
  • MCF-7 Cells
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism
  • RNA, Ribosomal / genetics
  • RNA, Ribosomal / metabolism*
  • RNA, Small Nucleolar / genetics
  • RNA, Small Nucleolar / metabolism
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*
  • ras Proteins / genetics
  • ras Proteins / metabolism


  • MYC protein, human
  • Nuclear Proteins
  • PNRC1 protein, human
  • Proto-Oncogene Proteins c-myc
  • RNA, Neoplasm
  • RNA, Ribosomal
  • RNA, Small Nucleolar
  • RNA, U3 small nucleolar
  • Trans-Activators
  • Transcription Factors
  • Tumor Suppressor Proteins
  • Endoribonucleases
  • DCP1A protein, human
  • DCP2 protein, human
  • ras Proteins