Potential for interdependent development of tRNA determinants for aminoacylation and ribosome decoding

Cuiping Liu, Howard Gamper, Hanqing Liu, Barry S. Cooperman and Ya-Ming Hou ()
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Cuiping Liu: Thomas Jefferson University
Howard Gamper: Thomas Jefferson University
Hanqing Liu: University of Pennsylvania
Barry S. Cooperman: University of Pennsylvania
Ya-Ming Hou: Thomas Jefferson University

Nature Communications, 2011, vol. 2, issue 1, 1-8

Abstract: 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 tRNACys, the fusion of a eukaryote-specific domain of human CysRS overcomes the cross-species barrier in human tRNACys. In addition to enabling recognition of the sequence differences in the tertiary core of tRNACys, the fused eukaryotic domain redirects the specificity of E. coli CysRS from the A37 present in bacterial tRNACys 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 tRNACys. These results raise the possibility of the development of tRNA nucleotide determinants for aminoacylation being interdependent with those for ribosome decoding.

Date: 2011
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DOI: 10.1038/ncomms1331

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