Regulation of global and specific mRNA translation by amino acids

A continuous supply of a complete complement of essential amino acids is a prerequisite for maintenance of optimal rates of protein synthesis in both liver and skeletal muscle. Deprivation of even a single essential amino acid causes a decrease in the synthesis of essentially all cellular proteins through an inhibition of the initiation phase of mRNA translation. However, the synthesis of all proteins is not repressed equally. Specific subsets of proteins, in particular those encoded by mRNAs containing a 5′-terminal oligopyrimidine (TOP) motif, are affected to a much greater extent than most proteins. The specific decrease in TOP mRNA translation is a result of an inhibition of the ribosomal protein S6 kinase, S6K1, and a concomitant decline in S6 phosphorylation. Interestingly, many TOP mRNAs encode proteins involved in mRNA translation, such as elongation factors eEF1A and eEF2, as well as the ribosomal proteins. Thus, deprivation of essential amino acids not only directly and rapidly represses global mRNA translation, but also potentially results in a reduction in the capacity to synthesize protein.