Translation mechanism and regulation: old players, new concepts

Abstract

The meeting on Translational Control and Non‐Coding RNA took place between 8 and 12 November 2006, in Nove Hrady, the Czech Republic, and was organized by M. Pospisek and L. Valasek. ![][1] Many pathways that regulate gene expression target the complex process of protein synthesis and in particular its initiation stage. During the past 40 years or so, all the initiation factors required for the assembly of translationally competent ribosomes have been identified and their principal roles determined. Recently, there has been significant progress in determining the structure of the components of the translation apparatus: from crystal structures of prokaryotic ribosomes, to crystal and nuclear magnetic resonance structures of factors, and cryo‐electron microscopy reconstructions of functional ribosomal complexes. These advances now allow the molecular mechanisms of the stages involved in initiation to be investigated in detail. Concurrently, diverse studies have revealed that translational control regulates processes ranging from development to learning. This meeting highlighted recent advances about canonical and internal ribosome entry site (IRES)‐mediated mechanisms of eukaryotic initiation, and the control of translation during development in response to stress and by mechanisms ranging from signal transduction pathways to regulation by noncoding RNAs and RNA‐binding proteins. Canonical 5′‐end‐dependent eukaryotic translation initiation requires at least 11 initiation factors (eIFs) and occurs in two stages: formation of the 48S initiation complex at the AUG codon of messenger RNA (mRNA), and its joining with a 60S ribosomal subunit (Fig 1; Hinnebusch et al , 2007; Pestova et al , 2007). eIF1 has a crucial role in the selection of initiation codons, allowing scanning 43S complexes to discriminate against codon–anticodon mismatches and preventing premature eIF5‐induced hydrolysis of eIF2‐bound GTP and Pi release. According to a recent model, eIF1—in cooperation with eIF1A—promotes a scanning‐competent ‘open’ conformation of the 43S complex. The establishment of codon–anticodon base‐pairing leads … [1]: /embed/graphic-1.gif