Translational control of protein synthesis: Implications for understanding changes in skeletal muscle mass

Gain or loss of skeletal muscle mass is due largely to the establishment of an imbalance between rates of protein synthesis and degradation. A key determinant of the rate of protein synthesis is translation initiation, a process regulated in part through binding of initiator methionyl-tRNA (met-tRNA_i) and messenger RNA (mRNA) to a 40S ribosomal subunit. Either the met-tRNA_i or mRNA binding step can become limiting for protein synthesis. Furthermore, the mRNA binding step can modulate translation of specific mRNAs with or without changes in the overall rate of protein synthesis. This report highlights molecular mechanisms involved in mediating control of the mRNA binding step in translation initiation. Particular attention is given to the effect of exercise on this step and to how the branched-chain amino acid leucine stimulates muscle protein synthesis after exercise. Potential mechanisms for exercise-induced increase in muscle mass are discussed.