ZNF692 organizes a hub specialized in 40S ribosomal subunit maturation enhancing translation in rapidly proliferating cells

Cell Rep. 2023 Oct 31;42(10):113280. doi: 10.1016/j.celrep.2023.113280. Epub 2023 Oct 16.

Abstract

Increased nucleolar size and activity correlate with aberrant ribosome biogenesis and enhanced translation in cancer cells. One of the first and rate-limiting steps in translation is the interaction of the 40S small ribosome subunit with mRNAs. Here, we report the identification of the zinc finger protein 692 (ZNF692), a MYC-induced nucleolar scaffold that coordinates the final steps in the biogenesis of the small ribosome subunit. ZNF692 forms a hub containing the exosome complex and ribosome biogenesis factors specialized in the final steps of 18S rRNA processing and 40S ribosome maturation in the granular component of the nucleolus. Highly proliferative cells are more reliant on ZNF692 than normal cells; thus, we conclude that effective production of small ribosome subunits is critical for translation efficiency in cancer cells.

Keywords: 40S; CP: Molecular biology; EXOSC7; EXOSC8; KRR1; MYC; ZNF692; exosome; nucleolus; rRNA; ribosome biogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Nucleolus / metabolism
  • DNA-Binding Proteins* / genetics
  • DNA-Binding Proteins* / metabolism
  • Humans
  • Protein Biosynthesis*
  • RNA, Ribosomal, 18S / genetics
  • RNA, Ribosomal, 18S / metabolism
  • Rats
  • Ribosomal Proteins* / metabolism
  • Ribosome Subunits, Small, Eukaryotic* / metabolism
  • Ribosomes / metabolism
  • Transcription Factors* / genetics
  • Transcription Factors* / metabolism

Substances

  • Ribosomal Proteins
  • RNA, Ribosomal, 18S
  • ZNF692 protein, human
  • DNA-Binding Proteins
  • Transcription Factors