title: Potential for interdependent development of tRNA determinants for aminoacylation and ribosome decoding.
abstract: Although the nucleotides in tRNA required for aminoacylation are conserved in evolution, bacterial aminoacyl-transfer RNA synthetases are unable to acylate eukaryotic tRNA. The cross-species barrier may be due to the absence of eukaryote-specific domains from bacterial aminoacyl-transfer RNA synthetases. Here we show that whereas Escherichia coli CysRS cannot acylate human tRNA(Cys), the fusion of a eukaryote-specific domain of human CysRS overcomes the cross-species barrier in human tRNA(Cys). In addition to enabling recognition of the sequence differences in the tertiary core of tRNA(Cys), the fused eukaryotic domain redirects the specificity of E. coli CysRS from the A37 present in bacterial tRNA(Cys) to the G37 in mammals. Further experiments show that the accuracy of codon recognition on the ribosome was also highly sensitive to the A37G transition in tRNA(Cys). These results raise the possibility of the development of tRNA nucleotide determinants for aminoacylation being interdependent with those for ribosome decoding.
authors.affiliation: Thomas Jefferson University, Department of Biochemistry and Molecular Biology, Philadelphia, Pennsylvania 19107, USA.
authors.forename: Cuiping
authors.initials: C
authors.lastname: Liu
authors.forename: Howard
authors.initials: H
authors.lastname: Gamper
authors.forename: Hanqing
authors.initials: H
authors.lastname: Liu
authors.forename: Barry S
authors.initials: BS
authors.lastname: Cooperman
authors.forename: Ya-Ming
authors.initials: YM
authors.lastname: Hou
mesh_terms: D000604:Amino Acyl-tRNA Synthetases / Q000737:chemistry / Q000502:physiology*; D001483:Base Sequence; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000502:physiology*; D019143:Evolution, Molecular; D042822:Genomic Instability; D006801:Humans; D007700:Kinetics; D009690:Nucleic Acid Conformation; D012343:RNA, Transfer / Q000737:chemistry*; D012350:RNA, Transfer, Cys / Q000737:chemistry / Q000378:metabolism*; D012270:Ribosomes / Q000502:physiology*; D013045:Species Specificity; D046249:Transfer RNA Aminoacylation
chemical_list: D029968:Escherichia coli Proteins; D012350:RNA, Transfer, Cys; D012343:RNA, Transfer; D000604:Amino Acyl-tRNA Synthetases