Signal Transduction in Ribosome Biogenesis: A Recipe to Avoid Disaster

Int J Mol Sci. 2019 Jun 3;20(11):2718. doi: 10.3390/ijms20112718.

Abstract

Energetically speaking, ribosome biogenesis is by far the most costly process of the cell and, therefore, must be highly regulated in order to avoid unnecessary energy expenditure. Not only must ribosomal RNA (rRNA) synthesis, ribosomal protein (RP) transcription, translation, and nuclear import, as well as ribosome assembly, be tightly controlled, these events must be coordinated with other cellular events, such as cell division and differentiation. In addition, ribosome biogenesis must respond rapidly to environmental cues mediated by internal and cell surface receptors, or stress (oxidative stress, DNA damage, amino acid depletion, etc.). This review examines some of the well-studied pathways known to control ribosome biogenesis (PI3K-AKT-mTOR, RB-p53, MYC) and how they may interact with some of the less well studied pathways (eIF2α kinase and RNA editing/splicing) in higher eukaryotes to regulate ribosome biogenesis, assembly, and protein translation in a dynamic manner.

Keywords: MYC; PI3K-AKT-mTOR; PKR-eIF2α; RNA editing; RNA polymerase; RNA splicing; TP53; nucleus; oncology; translation.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomarkers
  • Cell Cycle / genetics
  • Disease Susceptibility
  • Eukaryotic Initiation Factor-2 / metabolism
  • Extracellular Space / metabolism
  • Genes, myc
  • Humans
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Biosynthesis*
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA Editing
  • RNA Splicing
  • RNA, Ribosomal / genetics
  • RNA, Ribosomal / metabolism
  • Ribosomes / metabolism*
  • Signal Transduction*
  • Stress, Physiological
  • TOR Serine-Threonine Kinases / metabolism
  • Transcription, Genetic

Substances

  • Biomarkers
  • Eukaryotic Initiation Factor-2
  • RNA, Ribosomal
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases