Translational control in cellular and developmental processes

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. Translational regulation in cellular and developmental processes allows a rapid response to external signals and contributes to protein localization. The mechanisms of translational regulation are shared between these processes and occur at all stages of translation. 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.