Journal Article

Translational control of localized mRNAs: restricting protein synthesis in space and time

Besse, Florence, Ephrussi, Anne

2008

Overview

Key Points Recent genome-wide analyses in diverse organisms and cell types have revealed that a vast number of mRNAs display specific subcellular localization, and thus that mRNA localization coupled with precise translational control is a major mechanism used by cells to establish functionally distinct compartments and structures. Both the transport and translation of localizing mRNAs are regulated in the context of ribonucleoprotein (RNP) complexes of precise composition. These complexes start assembling in the nucleus and contain trans -acting regulatory factors, both proteins and non-coding RNAs. Translation of mRNAs that are in the process of being localized is blocked by a combination of translational repressors. These bind to their target mRNAs by recognizing specific cis -regulatory motifs. These repressors inhibit translation at various steps, but most block translation initiation. For many localizing mRNAs, translation is directly activated upon arrival at the final destination. This is commonly achieved by spatially restricted phosphorylation of translational repressors and a subsequent decrease in their affinity for target mRNAs. In some cell types, mainly neurons, translation of localized mRNAs is activated only in response to specific external signals. In this case, translational derepression is induced through conserved signalling pathways by regulation both of general components of the translational machinery and of mRNA-specific repressors. Decrypting the combinatorial code of cis -regulatory elements that dictate the specific behaviour of mRNAs is now one of the main challenges. The localization of mRNAs coupled with precise translational control is an important mechanism that is used by cells to establish functionally distinct compartments. Translation of localizing mRNAs is repressed by mechanisms that target translation initiation, and is derepressed following arrival at the final destination. As highlighted by recent genome-wide analyses in diverse organisms and cell types, subcellular targeting of mRNAs has emerged as a major mechanism for cells to establish functionally distinct compartments and structures. For protein synthesis to be spatially restricted, translation of localizing mRNAs is silenced during their transport and is activated when they reach their final destination. Such a precise translation pattern is controlled by repressors, which are specifically recruited to transport ribonucleoprotein particles and block translation at different steps. Functional studies have revealed that the inactivation of these repressors, either by pre-localized proteins or in response to conserved signalling pathways, triggers local protein synthesis.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: Animals / Biochemistry / Biology / Biomedical and Life Sciences / Cancer Research / Cell Biology / Cellular signal transduction / Control / Development Biology / Developmental Biology / Humans / Inactivation / Kinases / Life Sciences / Localization / Messenger RNA / Physiological aspects / Protein Biosynthesis / Protein synthesis / Proteins / review-article / Ribosomes / Ribosomes - metabolism / RNA / RNA - metabolism / RNA Transport / RNA Transport - physiology / RNA, Messenger / RNA, Messenger - metabolism / Stem Cells / Yeast