Control of the translational machinery by amino acids

Abstract

Amino acids are the precursors for the synthesis of proteins. In humans, approximately half of the 20 different amino acids are essential, ie, must be obtained from the diet. Cells must therefore take account of amino acid availability to achieve sustainable rates of protein synthesis. One of the major mechanisms involved in this is signaling through a complex of proteins termed mammalian target of rapamycin complex (mTORC) 1, which is activated by amino acids. In turn, mTORC1 regulates the production of ribosomes, the molecular machines that make proteins, and the activity of other cellular components required for protein synthesis. mTORC1 signaling promotes the transcription of the genes for ribosomal RNAs and many other components involved in ribosome production. It also positively regulates the translation of the messenger RNAs (mRNAs) for ribosomal proteins. Indeed, recent studies have shown that mammalian target of rapamycin signaling drives the translation of mRNAs for many anabolic enzymes and other proteins involved in diverse cellular functions. The translational machinery is also regulated by the absence of amino acids through the protein kinase GCN2 (general control nonrepressed 2), which phosphorylates and in end-effect inhibits the translation initiation factor eIF2 (eukaryotic initiation factor 2). This process shuts down general protein synthesis to conserve amino acids.