New functions for amino acids: effects on gene transcription and translation

Amino acids act to regulate multiple processes related to gene expression, including modulation of the function of the proteins that mediate messenger RNA (mRNA) translation. By modulating the function of translation initiation and elongation factors, amino acids regulate the translation of mRNA on a global scale and also act to cause preferential changes in the translation of mRNAs encoding particular proteins or families of proteins. However, amino acids do not directly regulate the function of translation initiation and elongation factors, but instead modulate signaling through pathways traditionally considered to be solely involved in mediating the action of hormones. The best-characterized example of amino acid-induced regulation of a signal transduction pathway is one involving a protein kinase referred to as the mammalian target of rapamycin (mTOR), through which the branched-chain amino acids, particularly leucine, act to modulate the function of proteins engaged in both global mRNA translation and the selection of specific mRNAs for translation. Less understood at this point in time is evidence suggesting that amino acids also act to regulate mRNA translation through mTOR-independent mechanisms. The goal of the present review is to briefly summarize studies, primarily those performed in the laboratories of the authors, that focus on the role of the branched-chain amino acids in the regulation of mRNA translation in skeletal muscle.