title: Trans-editing of mischarged tRNAs.
abstract: Aminoacyl-tRNA synthetases (aaRSs) are multidomain proteins that specifically attach amino acids to their cognate tRNAs. Their most conserved, and presumably evolutionarily oldest, domains are the catalytic cores, which activate amino acids and transfer them to the 3' ends of tRNAs. Additional domains appended to or inserted in the body of aaRSs increase efficiency and specificity of the aminoacylation process, either by providing additional tRNA contacts, or by hydrolyzing noncognate amino acid products (cis-editing). Here, we report specific tRNA-dependent trans-editing by aaRS-like proteins that reciprocate the editing domains of aaRSs, but not the remainder of the corresponding enzyme. A freestanding homologue of the prolyl-tRNA synthetase-editing domain, the PrdX protein from Clostridium sticklandii, efficiently and specifically hydrolyzes Ala-tRNAPro. Similarly, autonomous alanyl-tRNA synthetase-editing domain homologues (AlaX proteins) from Methanosarcina barkeri and Sulfolobus solfataricus hydrolyze Ser-tRNAAla and Gly-tRNAAla substrates. The discovery of autonomous editing proteins efficient in hydrolyzing misacylated products provides a direct link between ancestral aaRSs consisting solely of the catalytic core and extant enzymes to which functionally independent modules are appended.
authors.affiliation: Department of Molecular Biophysics, Yale University, New Haven, CT 06520-8114, USA.
authors.forename: Ivan
authors.initials: I
authors.lastname: Ahel
authors.forename: Dragana
authors.initials: D
authors.lastname: Korencic
authors.forename: Michael
authors.initials: M
authors.lastname: Ibba
authors.forename: Dieter
authors.initials: D
authors.lastname: Söll
mesh_terms: D000595:Amino Acid Sequence; D000604:Amino Acyl-tRNA Synthetases / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D001419:Bacteria / Q000145:classification / Q000201:enzymology / Q000235:genetics; D001665:Binding Sites; D006868:Hydrolysis; D008969:Molecular Sequence Data; D010802:Phylogeny; D017393:RNA Editing / Q000235:genetics*; D012343:RNA, Transfer / Q000235:genetics*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D012343:RNA, Transfer; D000604:Amino Acyl-tRNA Synthetases