title: Quality control in tRNA charging.
abstract: Faithful translation of the genetic code during protein synthesis is fundamental to the growth, development, and function of living organisms. Aminoacyl-tRNA synthetases (AARSs), which define the genetic code by correctly pairing amino acids with their cognate tRNAs, are responsible for 'quality control' in the flow of information from a gene to a protein. When differences in binding energies of amino acids to an AARS are inadequate, editing is used to achieve high selectivity. Editing occurs at the synthetic active site by hydrolysis of noncognate aminoacyl-adenylates (pretransfer editing) and at a dedicated editing site located in a separate domain by deacylation of mischarged aminoacyl-tRNA (posttransfer editing). Access of nonprotein amino acids, such as homocysteine or ornithine, to the genetic code is prevented by the editing function of AARSs, which functionally partitions amino acids present in living cells into protein and nonprotein amino acids. Continuous editing is part of the tRNA aminoacylation process in living organisms from bacteria to human beings. Preventing mistranslation by the clearance of misactivated amino acids is crucial to cellular homeostasis and has a role in etiology of disease. Although there is a strong selective pressure to minimize mistranslation, some organisms possess error-prone AARSs that cause mistranslation. Elevated levels of mistranslation and the synthesis of statistical proteins can be beneficial for pathogens by increasing phenotypic variation essential for the evasion of host defenses.
authors.affiliation: Department of Microbiology and Molecular Genetics, UMDNJ-New Jersey Medical School, International Center for Public Health, Newark, NJ, USA. jakubows@umdnj.edu
authors.forename: Hieronim
authors.initials: H
authors.lastname: Jakubowski
mesh_terms: D000604:Amino Acyl-tRNA Synthetases / Q000737:chemistry / Q000378:metabolism; D001927:Brain Diseases / Q000209:etiology; D020134:Catalytic Domain; D006710:Homocysteine / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications; D014176:Protein Biosynthesis; D017393:RNA Editing / Q000502:physiology; D012343:RNA, Transfer / Q000378:metabolism*; D013379:Substrate Specificity; D046249:Transfer RNA Aminoacylation
chemical_list: D006710:Homocysteine; D012343:RNA, Transfer; D000604:Amino Acyl-tRNA Synthetases