Protein synthesis (also termed mRNA translation) is a key step in the expression of a cell's genetic information, in which the information contained within the coding region of the mRNA is used to direct the synthesis of the new protein, a process that is catalysed by the ribosome. Protein synthesis must be tightly controlled, to ensure the right proteins are made in the right amounts at the right time, and must be accurate, to avoid errors that could lead to the production of defective and potentially damaging proteins. In addition to the ribosome, protein synthesis also requires proteins termed translation factors, which mediate specific steps of the process. The first major stage of mRNA translation is termed ‘initiation’ and involves the recruitment of the ribosome to the mRNA and the identification of the correct start codon to commence translation. In eukaryotic cells, this process requires a set of eIFs (eukaryotic initiation factors). During the second main stage of translation, ‘elongation’, the ribosome traverses the coding region of the mRNA, assembling the new polypeptide: this process requires eEFs (eukaryotic elongation factors). Control of eEF2 is important in certain neurological processes. It is now clear that defects in eIFs or in their control can give rise to a number of diseases. This paper provides an overview of translation initiation and its control mechanisms, particularly those examined in neuronal cells. A major focus concerns an inherited neurological condition termed VHM (vanishing white matter) or CACH (childhood ataxia with central nervous system hypomyelination). VWM/CACH is caused by mutations in the translation initiation factor, eIF2B, a component of the basal translational machinery in all cells.

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