Regulation of mRNA translation during mitosis

Elife. 2015 Aug 25:4:e07957. doi: 10.7554/eLife.07957.

Abstract

Passage through mitosis is driven by precisely-timed changes in transcriptional regulation and protein degradation. However, the importance of translational regulation during mitosis remains poorly understood. Here, using ribosome profiling, we find both a global translational repression and identified ~200 mRNAs that undergo specific translational regulation at mitotic entry. In contrast, few changes in mRNA abundance are observed, indicating that regulation of translation is the primary mechanism of modulating protein expression during mitosis. Interestingly, 91% of the mRNAs that undergo gene-specific regulation in mitosis are translationally repressed, rather than activated. One of the most pronounced translationally-repressed genes is Emi1, an inhibitor of the anaphase promoting complex (APC) which is degraded during mitosis. We show that full APC activation requires translational repression of Emi1 in addition to its degradation. These results identify gene-specific translational repression as a means of controlling the mitotic proteome, which may complement post-translational mechanisms for inactivating protein function.

Keywords: APC; Emi1; cell biology; computational biology; human; mRNA; mitosis; ribosone profiling; systems biology; translation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaphase-Promoting Complex-Cyclosome / metabolism
  • Cell Cycle Proteins / metabolism
  • Cell Line
  • Epithelial Cells / physiology
  • F-Box Proteins / metabolism
  • Gene Expression Regulation*
  • Humans
  • Mitosis*
  • Protein Biosynthesis*
  • Proteolysis

Substances

  • Cell Cycle Proteins
  • F-Box Proteins
  • FBXO5 protein, human
  • Anaphase-Promoting Complex-Cyclosome