Article

A T-stem slip in human mitochondrial tRNALeu(CUN) governs its charging capacity.

State Key Laboratory of Molecular Biology, Shanghai Institutes for Biological Sciences, The Chinese Academy of Sciences 320 Yue Yang Road, Shanghai 200031, People's Republic of China.
Nucleic Acids Research (Impact Factor: 8.81). 02/2005; 33(11):3606-13. DOI: 10.1093/nar/gki677
Source: PubMed

ABSTRACT The human mitochondrial tRNALeu(CUN) [hmtRNALeu(CUN)] corresponds to the most abundant codon for leucine in human mitochondrial protein genes. Here, in vitro studies reveal that the U48C substitution in hmtRNALeu(CUN), which corresponds to the pathological T12311C gene mutation, improved the aminoacylation efficiency of hmtRNALeu(CUN). Enzymatic probing suggested a more flexible secondary structure in the wild-type hmtRNALeu(CUN) transcript compared with the U48C mutant. Structural analysis revealed that the flexibility of hmtRNALeu(CUN) facilitates a T-stem slip resulting in two potential tertiary structures. Several rationally designed tRNALeu(CUN) mutants were generated to examine the structural and functional consequences of the T-stem slip. Examination of these hmtRNALeu(CUN) mutants indicated that the T-stem slip governs tRNA accepting activity. These results suggest a novel, self-regulation mechanism of tRNA structure and function.

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