A translation-like cycle is a quality control checkpoint for maturing 40S ribosome subunits

Cell. 2012 Jul 6;150(1):111-21. doi: 10.1016/j.cell.2012.04.044.

Abstract

Assembly factors (AFs) prevent premature translation initiation on small (40S) ribosomal subunit assembly intermediates by blocking ligand binding. However, it is unclear how AFs are displaced from maturing 40S ribosomes, if or how maturing subunits are assessed for fidelity, and what prevents premature translation initiation once AFs dissociate. Here we show that maturation involves a translation-like cycle whereby the translation factor eIF5B, a GTPase, promotes joining of large (60S) subunits with pre-40S subunits to give 80S-like complexes, which are subsequently disassembled by the termination factor Rli1, an ATPase. The AFs Tsr1 and Rio2 block the mRNA channel and initiator tRNA binding site, and therefore 80S-like ribosomes lack mRNA or initiator tRNA. After Tsr1 and Rio2 dissociate from 80S-like complexes Rli1-directed displacement of 60S subunits allows for translation initiation. This cycle thus provides a functional test of 60S subunit binding and the GTPase site before ribosomes enter the translating pool.

Publication types

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

MeSH terms

  • ATP-Binding Cassette Transporters / metabolism
  • Adenylate Kinase / metabolism
  • Binding Sites
  • Cell Cycle Proteins / metabolism
  • Endoribonucleases / metabolism
  • Eukaryotic Initiation Factors / metabolism
  • GTP Phosphohydrolases / metabolism
  • Nuclear Proteins / metabolism
  • Nucleoside-Triphosphatase / metabolism
  • Protein Biosynthesis*
  • Ribosome Subunits, Large, Eukaryotic / metabolism
  • Ribosome Subunits, Small, Eukaryotic / metabolism*
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / metabolism

Substances

  • ATP-Binding Cassette Transporters
  • Cell Cycle Proteins
  • Eukaryotic Initiation Factors
  • Nuclear Proteins
  • RLI1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • eukaryotic initiation factor-5B
  • Adenylate Kinase
  • FAP7 protein, S cerevisiae
  • Dom34 protein, S cerevisiae
  • Endoribonucleases
  • GTP Phosphohydrolases
  • Nucleoside-Triphosphatase