Ribosome Has A Third Fidelity Trick Up Its Sleeve

The high accuracy of ribosomal protein synthesis was believed to rely on the fidelity of two key biosynthetic steps, but a research team has found that a previously unknown step is a third important contributor to the fidelity of the process (Nature 2009, 457, 161). The two known steps on which mistake-free protein synthesis depends are the enzymatic addition of correct amino acids to each of the amino acid-specific transfer RNAs and the ribosome's selection of tRNAs that match up properly with each three-residue coding unit of messenger RNA. Both steps occur before peptide bond formation, the process by which amino acids are snapped onto growing proteins. Hani S. Zaher and Rachel Green of the Johns Hopkins University School of Medicine now report that the ribosome senses the incorporation of an incorrect amino acid and starts a process that leads to premature termination of the misspelled protein molecule's biosynthesis. This step, which occurs after peptide bond formation, may contribute close to an order of magnitude enhancement to the fidelity of protein synthesis, the researchers note.