Cell-Cycle-Dependent Regulation of Translation: New Interpretations of Old Observations in Light of New Approaches

Bioessays. 2019 Aug;41(8):e1900022. doi: 10.1002/bies.201900022. Epub 2019 Jun 18.

Abstract

It is a long-standing view that global translation varies during the cell cycle and is much lower in mitosis than in other cell-cycle phases. However, the central papers in the literature are not in agreement about the extent of downregulation in mitosis, ranging from a dramatic decrease to only a marginal reduction. Herein, it is argued that the discrepancy derives from technical challenges. Cell-cycle-dependent variations are most conveniently studied in synchronized cells, but the synchronization methods by themselves often evoke stress responses that, in turn, affect translation rates. Further, it is argued that previously reported cell-cycle-dependent changes in the global translation rate to a large extent reflect responses to the synchronization methods. Recent findings strongly suggest that the global translation rate is not regulated in a cell-cycle-dependent manner. Novel techniques allowing a genome-wide analysis of translational profiles suggest that the extent and importance of selective translational regulation associated with cell-cycle transitions have been underestimated. Therefore, the main question is which messenger RNAs (mRNAs) are translated, rather than whether the global translation rate is decreased.

Keywords: 4E-BP phosphorylation; cell cycle; cell-cycle synchronization; eIF2α phosphorylation; selective translation; translation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions / physiology
  • Animals
  • Cell Cycle Checkpoints / physiology*
  • Eukaryotic Initiation Factor-2 / metabolism
  • Humans
  • Mitosis / physiology
  • Phosphorylation
  • Protein Biosynthesis / physiology*
  • RNA, Messenger / metabolism*
  • RNA, Transfer / metabolism
  • Ribosomes / metabolism
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / metabolism

Substances

  • 5' Untranslated Regions
  • Eukaryotic Initiation Factor-2
  • RNA, Messenger
  • SUI2 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • RNA, Transfer