engleski

Quality control in nature: the role of aminoacyl-tRNA synthetases

Translation is the process by which the genetic information contained in mRNA is used to determine the sequential order of amino acids in a protein. Experimental measurements have suggested that, overall, an amino acid is misincoroprated at the rate of about 1 in every 10,000 codons. This high level of fidelity is ensured by various types of proofreading and editing mechanisms used throughout protein biosynthesis. The maturation of tRNAs and mRNAs is monitored, as is the identity of amino acids attached to tRNAs. Accuracy is further enhanced during the selection of aminoacyl-tRNAs on the ribosome and their base pairing with mRNA. Recent studies have begun to reveal the molecular basis of quality control processes which are essential for faithful translation. Aminoacyl-tRNA synthetases are the only components of the gene expression machinery that function on the interface between the nucleic acids and proteins. These enzymes catalyze esterification of tRNAs with cognate amino acids and display high level of substrate specificity. During substrate selection tRNA first binds the aminoacyl-tRNA synthetase, either as a free enzyme or as an enzyme – aminoacyl-adenylate complex. The recognition is governed by sequence-specific protein-RNA interactions. Then, this transient protein RNA-complex catalyzes attachment of the amino acid to the 3´-terminal adenosine of the tRNA. While the differences of the side chains of amino acids are often sufficient to allow their specific binding, selection of the correct tRNA is assumed to occur as a result of preferential reaction kinetics for cognate protein-RNA complexes. The quality of aminoacyl-tRNA synthesis in the cell can be further improved in two ways: by the mechanisms that enhance the accuracy of substrate selection or by corrective mechanisms. The first ones are generally based on conformational changes in either enzyme or tRNA, induced by macromolecular complex formation or interaction with a non-synthetase protein. On the other hand, some synthetases exhibit hydrolytic activities that prevent the transfer of misactivated amino acid or the release of incorrectly aminoacylated tRNAs. Corrective mechanisms are disfavored in the cell because they are energetically more costly. Thus, maximum accuracy, owing to its high energy cost, is never achieved by a living cell. Our recent studies have revealed that accurate seryl-tRNA synthesis in different organisms and cellular compartments is accomplished via tRNA-assisted optimization of amino acid binding to the enzyme active site. A non-synthetase protein partner may be involved in this process.

quality control in translation; aminoacyl-tRNA synthetases

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