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Translational control in cellular and developmental processes

Nature Reviews Genetics volume 13, pages 383–394 (2012)Cite this article

Subjects

Key Points

  • Translational control is a widespread means of regulating gene expression in development and cellular processes. It enables highly dynamic responses to external signals and contributes to protein targeting.

  • Translational control mechanisms target many steps of protein synthesis and influence many components of the core translational machinery.

  • Eukaryotic translation initiation factor 4E (eIF4E), an initiation factor that recognizes the 5′ cap structure of mRNA and assembles a complex that is necessary for ribosome recruitment, is targeted by translational repressors called eIF4E-binding proteins (4EBPs). 4EBPs are implicated in numerous cellular, developmental and physiological processes.

  • Many other translational regulators operate through effects on the poly(A) tail length of targeted mRNAs, and others affect later steps of translation, such as subunit joining and elongation. Some translational repressors operate by sequestering mRNAs into inactive RNA granules.

  • Localization of mRNA often complements translational control by concentrating the mRNA in a cytoplasmic space where it is translationally active.

  • Defects in translational control have been linked to many human diseases, indicating its central role in developmental and cellular processes.

Abstract

Growing evidence indicates that translational control of specific mRNAs contributes importantly to genetic regulation across the breadth of cellular and developmental processes. Synthesis of protein from a specific mRNA can be controlled by RNA-binding proteins at the level of translational initiation and elongation, and translational control is also sometimes coupled to mRNA localization mechanisms. Recent discoveries from invertebrate and vertebrate systems have uncovered novel modes of translational regulation, have provided new insights into how specific regulators target the general translational machinery and have identified several new links between translational control and human disease.

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Figure 1: An overview of cap-dependent translation initiation.
Figure 2: Three mechanisms for regulating translation of specific mRNAs.
Figure 3: The mTORC1 pathway influences translation.
Figure 4: Linking mRNAs to motor proteins for localization.

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  1. Department of Biology, McGill University, 3649 Promenade Sir William Osler, Montreal, H3G 0T5, Quebec, Canada

    Jian Kong & Paul Lasko

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  1. Jian Kong
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Correspondence to Paul Lasko.

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Glossary

5′ cap structure

A 7-methylguanosine residue that is enzymatically added to the 5′ end of an mRNA and linked through a 5′–5′ triphosphate bridge.

Mammalian target of rapamycin complex 1

(mTORC1). A signalling complex that senses nutrient abundance and regulates cell growth and proliferation accordingly.

Pachytene

The stage during the first meiotic division when chromosomal crossing-over and recombination occurs.

Synaptonemal complex

A protein structure that forms between homologous chromosomes during the first meiotic prophase and that facilitates chromosome pairing.

Ribonucleoproteins

Multimolecular complexes that contain both RNAs and proteins.

Heterogeneous nuclear ribonucleoprotein E1

(hnRNPE1). An RNA-binding protein with functions in precursor mRNA processing and in regulating mRNA stability and translation. Despite its name, it is present and functional both in nuclei and in the cytoplasm.

Polyribosomes

Actively translated mRNAs that are associated with multiple ribosomes, each elongating a different nascent polypeptide chain.

High-throughput sequencing coupled with crosslinking and immunoprecipitation

(HITS–CLIP). A technique in which mRNAs associated with a particular protein or in a ribonucleoprotein complex are recovered by co-immunoprecipitation and analysed by deep sequencing.

Normoxia

A physiological condition in which oxygen levels are sufficient and not limiting for metabolic processes.

MDM2

An E3 ubiquitin ligase that recognizes and destabilizes p53.

Prader–Willi syndrome

A rare genetic disorder that results in obesity and reductions in muscle tone, cognitive capacity and production of sex hormones.

Homeotic transformation

In developmental biology, a situation that is often caused by a mutation or an alteration in gene expression whereby precursors to a particular cell, tissue or organ type develop instead into a different one.

Homeobox gene

(HOX gene). One of a set of genes that encodes a particular type of transcription factor and that is implicated in establishing many developmental fates, including the identity of body segments along the anterior–posterior axis.

Processing bodies

Also called P bodies, these constitute a type of RNA granule that is linked to cytoplasmic RNA decay pathways.

Ribosome profiling

A technique for measuring translation of many species of mRNA simultaneously in vivo.

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Kong, J., Lasko, P. Translational control in cellular and developmental processes. Nat Rev Genet 13, 383–394 (2012). https://doi.org/10.1038/nrg3184

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