Over the past 20 years, mRNA targeting coupled to local translation has been recognized as a powerful means to spatially restrict the synthesis of specific proteins in cells. In particular, for proteins that can be deleterious to the cell when expressed ectopically, the ability to precisely restrict their synthesis has obvious impor- tance 1 . Furthermore, transcript localization allows for the superimposition of multiple layers of control. The prevalence of this phenomenon has become apparent with the advent of genome-wide analyses in diverse organisms and cell types (Supplementary information S1 (table)). These studies have revealed that a vast number of mRNAs display specific subcellular localizations (for example, apical–basal, membrane associated, centro- some, spindle pole or astral-microtubule associated), which indicates that mRNA localization is an important mechanism that is used by cells to establish functionally distinct compartments and structures 2 . What is the purpose of localizing mRNAs? Answers can be found in diverse types of somatic cells, most of which display some form of polarization and functional compartmentalization. For instance, whereas much is known about the composition of the complexes that establish and maintain epithelial cell polarity, an out- standing issue is that of how their individual protein com- ponents, many of them cytoplasmic, achieve their apical or basolateral membrane localization. Recent genetic studies have revealed that mRNAs that encode two key polarity regulators, Stardust and Crumbs (both are com- ponents of the conserved apical Crumbs–Stardust–PATJ complex), are localized apically, thus contributing to the establishment of epithelial cell polarity 3,4 . Localized mRNAs also regulate directed cell migration. In fibro- blasts, the localization of β-actin mRNA coupled with its translation at the leading edge promotes local cytoskeletal assembly, cell polarization and directional movement 5 . Similarly, during neuronal development, axonal growth cones are guided by external cues that induce local syn- thesis of cytoskeleton regulators 6 . Semaphorin-3A, for example, provokes growth cone collapse, which triggers local translation of axonally targeted RHOA mRNA 7 . In differentiated neurons, up to hundreds of mRNAs are dendritically enriched, as estimated from primary cultures (Supplementary information S1 (table)). Local and specific translation of a subset of these mRNAs can allow rapid and synapse-restricted responses to neuronal stimulation 8 . Segregation of cell fate and embryonic polar- ity determinants is also frequently achieved by mRNA localization coupled to local translation 9–11 . Among the best-studied examples is ASH1 mRNA localization to the tip of the daughter cell in the budding yeast Saccharomyces cerevisiae (FIG. 1). Localization-dependent translational activation of ASH1 mRNA, which encodes a repressor of mating-type switching, ensures its restriction to the daughter cell and thus the generation of two cells of distinct types, a prerequisite for mating 11,12 . Localizing mRNAs are packaged into ribonucleo- protein complexes (RNP complexes) that engage with cytoskeletal motors for directed transport along cyto- skeletal tracks (BOX 1) and ensure their translational *European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany. ‡ Institute of Developmental Biology and Cancer, CNRS UMR6543, University of Nice Sophia Antipolis, Parc Valrose, 06108 Nice cedex 2, France. e-mails: besse@unice.fr; ephrussi@embl.de doi:10.1038/nrm2548 Ribonucleoprotein complex A multimolecular complex that is composed of mRNAs and associated trans-acting factors (proteins or non-coding RNAs). Translational control of localized mRNAs: restricting protein synthesis in space and time Florence Besse* ‡ and Anne Ephrussi* Abstract | 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. Post-transcriPtional control REVIEWS NATURE REVIEWS | molecular cell biology VOLUME 9 | DECEMBER 2008 | 971