Synthesis of the translational apparatus is regulated at the translational level

Oded Meyuhas*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

449 Scopus citations

Abstract

The synthesis of many mammalian proteins associated with the translational apparatus is selectively regulated by mitogenic and nutritional stimuli, at the translational level. The apparent advantages of the regulation of gene expression at the translational level are the speed and the readily reversible nature of the response to altering physiological conditions. These two features enable cells to rapidly repress the biosynthesis of the translational machinery upon shortage of amino acids or growth arrest, thus rapidly blocking unnecessary energy wastage. Likewise, when amino acids are replenished or mitogenic stimulation is applied, then cells can rapidly respond in resuming the costly biosynthesis of the translational apparatus. A structural hallmark, common to mRNAs encoding many components of the translational machinery, is the presence of a 5' terminal oligopyrimidine tract (5'TOP), referred to as TOP mRNAs. This structural motif comprises the core of the translational cis-regulatory element of these mRNAs. The present review focuses on the mechanism underlying the translational control of TOP mRNAs upon growth and nutritional stimuli. A special emphasis is put on the pivotal role played by ribosomal protein S6 kinase (S6K) in this mode of regulation, and the upstream regulatory pathways, which might be engaged in transducing external signals into activation of S6K. Finally, the possible involvement of pyrimidine-binding proteins in the translational control of TOP mRNAs is discussed.

Original languageEnglish
Pages (from-to)6321-6330
Number of pages10
JournalEuropean Journal of Biochemistry
Volume267
Issue number21
DOIs
StatePublished - 2000

Keywords

  • 5' terminal oligopyrimidine tract (5'TOP)
  • Amino-acid starvation
  • Growth arrest
  • Mammalian target of rapamycin (mTOR)
  • Phosphatidylinositol 3-kinase (PtdIns 3-kinase)
  • Phosphoinositide-dependent kinase 1 (PDK1)
  • Ribosomal protein S6 kinase (S6K)
  • TOP mRNAs
  • Translational apparatus
  • Translational control

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