The final step of 40S ribosomal subunit maturation is controlled by a dual key lock

Elife. 2021 Apr 28:10:e61254. doi: 10.7554/eLife.61254.


Preventing premature interaction of pre-ribosomes with the translation apparatus is essential for translational accuracy. Hence, the final maturation step releasing functional 40S ribosomal subunits, namely processing of the 18S ribosomal RNA 3' end, is safeguarded by the protein DIM2, which both interacts with the endoribonuclease NOB1 and masks the rRNA cleavage site. To elucidate the control mechanism that unlocks NOB1 activity, we performed cryo-electron microscopy analysis of late human pre-40S particles purified using a catalytically inactive form of the ATPase RIO1. These structures, together with in vivo and in vitro functional analyses, support a model in which ATP-loaded RIO1 cooperates with ribosomal protein RPS26/eS26 to displace DIM2 from the 18S rRNA 3' end, thereby triggering final cleavage by NOB1; release of ADP then leads to RIO1 dissociation from the 40S subunit. This dual key lock mechanism requiring RIO1 and RPS26 guarantees the precise timing of pre-40S particle conversion into translation-competent ribosomal subunits.

Keywords: chromosomes; cryo-EM; gene expression; human; human ribosome biogenesis; molecular biophysics; pre-rRNA processing; small ribosomal subunit; structural biology; structure-function study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Humans
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Ribosomal Proteins / genetics
  • Ribosomal Proteins / metabolism*
  • Ribosome Subunits, Small, Eukaryotic / genetics
  • Ribosome Subunits, Small, Eukaryotic / metabolism*


  • Cell Cycle Proteins
  • NOB1 protein, human
  • Nuclear Proteins
  • RNA-Binding Proteins
  • RPS26 protein, human
  • Ribosomal Proteins
  • TXNL4B protein, human
  • Protein Serine-Threonine Kinases
  • RIOK1 protein, human

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.