Amino acids as regulators of gene expression

Recent advances in biomedical research reveal a key role for amino acids as nutritional signals in the regulation of a number of cellular processes. Studies employing a variety of cell types and different tissues demonstrate that one such process affected is the regulation of gene expression through modulation of the translation of messenger RNA (mRNA). The studies show that cells recognize changes in amino acid availability and generate alterations in signal transduction pathways that are also regulated by hormones and growth factors. The cells then respond to the integrated signaling input by either upregulating or downregulating translation initiation, i.e., the process during which initiator methionyl-tRNA (met-tRNAi) and mRNA bind to a 40S ribosomal subunit followed by the joining of a 60S ribosomal subunit to form a translationally competent 80S ribosome. The response of translation initiation to a change in amino acid and/or hormone availability can be general, i.e., affecting the translation of most if not all mRNAs, and/or specific, i.e., affecting the translation of a single class or subset of mRNAs. Both the general and specific responses can be mediated through regulation of either the met-tRNAi and/or mRNA binding steps. The specific response may also involve an additional regulatory site, i.e., the phosphorylation status of ribosomal protein rpS6, one of the proteins composing the 40S ribosomal subunit. Learning how the cell recognizes a sufficiency of amino acids is presently the objective of intense research. Present evidence, however, suggests multiple recognition sites and multiple signaling pathways. Below, we summarize our current knowledge of the signaling pathways known to respond to changes in amino acid availability. In addition, the translation initiation factors and mRNA structural elements that are involved in changes in both global and specific modulation of mRNA translation are discussed.The first step in translation initiation involves