Translational control of eukaryotic gene expression

Abstract

Translational control mechanisms are, besides transcriptional control and mRNA stability, the most determining for final protein levels. A large number of accessory factors that assist the ribosome during initiation, elongation, and termination of translation are required for protein synthesis. Cap-dependent translational control occurs mainly during the initiation step, involving eukaryotic initiation factors (eIFs) and accessory proteins. Initiation is affected by various stimuli that influence the phosphorylation status of both eIF4E and eIF2 and through binding of 4E-binding proteins to eIF4E, which finally inhibits cap- dependent translation. Under conditions where cap-dependent translation is hampered, translation of transcripts containing an internal ribosome entry site can still be supported in a cap-independent manner. An interesting example of translational control is the switch between cap-independent and cap-dependent translation during the eukaryotic cell cycle. At the G1-to-S transition, translation occurs predominantly in a cap-dependent manner, while during the G2-to-M transition, cap-dependent translation is inhibited and transcripts are predominantly translated through a cap-independent mechanism.

Keywords::

• Initiation of translation
• posttranscriptional regulation
• IRES
• cell cycle

Acknowledgments

The authors thank Frank Van Breusegem for critical reading of the manuscript and Martine De Cock for help in preparing it. This work was supported by grants from the Interuniversity Attraction Poles Programme (IUAP VI/33), initiated by the Belgian State, Science Policy Office and the Research Foundation-Flanders (grant no. G.0025.02).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Editor: Michael M. Cox