Ubiquitin-dependent translation control mechanisms: Degradation and beyond

Cell Rep. 2024 Dec 24;43(12):115050. doi: 10.1016/j.celrep.2024.115050. Epub 2024 Dec 10.

Abstract

Translation control mechanisms connect the largely static genome to the highly dynamic proteome. At each step in the translation cycle, multiple layers of regulation enable efficient protein biogenesis under optimal conditions and mediate responses to acute environmental challenges. Recent research has demonstrated that individual ribosomal protein ubiquitylation events act as molecular signals to specify quality control pathway outcomes. Here, we synthesize current knowledge of ubiquitin-mediated translation control mechanisms and highlight key outstanding questions. We compare and contrast ubiquitin-dependent mechanisms that regulate ribosome-associated quality control pathways at several steps in the translation cycle. We also explore how distinct ribosome ubiquitylation events on specific ribosomal proteins impact translation activity and how defects in specific ubiquitin-mediated regulatory steps impact physiology and health.

Keywords: CP: Molecular biology; NRD; eukaryotic translation; mRNA decay; non-functional rRNA decay; proteostasis; ribosomal protein degradation; ribosomal ubiquitylation; ribosome biogenesis; ribosome-associated quality control; translation regulation; translation stress response; translation surveillance pathways.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Protein Biosynthesis*
  • Proteolysis
  • Ribosomal Proteins / genetics
  • Ribosomal Proteins / metabolism
  • Ribosomes* / metabolism
  • Ubiquitin* / metabolism
  • Ubiquitination*

Substances

  • Ubiquitin
  • Ribosomal Proteins