Transfer RNA Recognition and Aminoacylation by Synthetases

Abstract Fidelity of transfer ribonucleic acid (tRNA) charging by amino acids ensures correct translation of the genetic code into proteins. Charging is catalysed by a set of enzymes known as aminoacyl‐tRNA synthetases. Owing to the degeneracy of the genetic code, some of the different tRNAs have the same amino acids attached to them. Specificity of charging obeys universal rules and is ensured by positive elements, the identity determinants unique to each tRNA and responsible for its recognition by the cognate synthetase, and negative elements, the antideterminants that prevent false recognitions. To fulfil the aminoacylation specificity and prevent noncognate aminoacyl‐tRNA delivery to the ribosome, some synthetases also mediate proofreading reactions that increase fidelity of the tRNA charging. In such reactions, misactivated amino acids or mischarged tRNAs are checked in specific sites, and noncognate products are hydrolysed. However, mischarging is beneficial under certain stress circumstances or when catalysed by nondiscriminatory synthetases and represents a driving force in evolution. Key Concepts Translational expression of the genetic code refers to aminoacyl‐tRNA‐ and ribosome‐dependent decoding of genes into proteins, a process highly dependent on fidelity of tRNA aminoacylation by synthetases. The rules that account for the aminoacylation identity of tRNAs are referred to as the second genetic code. The RNA operational code is encoded in the acceptor stem of tRNA and is crucial for recognition by aminoacyl‐tRNA synthetases and specific aminoacylation. Allostery in tRNA–synthetase systems concerns long‐range transfer of chemical information (up to 75 Å) to the synthetase catalytic site (through the body of tRNA and/or synthetase) triggered by contacts of tRNA identity determinants with the synthetase. Engineering the identity of tRNA–synthetase systems allows reprogramming the genetic code.