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An unusual tRNAThr derived from tRNAHis reassigns in yeast mitochondria the CUN codons to threonine

Author:
Su, Dan, Lieberman, Allyson, Lang, B. Franz, Simonović, Miljan, Söll, Dieter, Ling, Jiqiang
Source:
Nucleic acids research 2011 v.39 no.11 pp. 4866-4874
ISSN:
0305-1048
Subject:
Candida albicans, Saccharomyces cerevisiae, codons, coevolution, genes, genetic code, histidine-tRNA ligase, leucine, mitochondria, phylogeny, threonine, threonine-tRNA ligase, transfer RNA, yeasts
Abstract:
The standard genetic code is used by most living organisms, yet deviations have been observed in many genomes, suggesting that the genetic code has been evolving. In certain yeast mitochondria, CUN codons are reassigned from leucine to threonine, which requires an unusual tRNAThr with an enlarged 8-nt anticodon loop (Formula ). To trace its evolutionary origin we performed a comprehensive phylogenetic analysis which revealed that Formula evolved from yeast mitochondrial tRNAHis. To understand this tRNA identity change, we performed mutational and biochemical experiments. We show that Saccharomyces cerevisiae mitochondrial threonyl-tRNA synthetase (MST1) could attach threonine to both Formula and the regular Formula , but not to the wild-type tRNAHis. A loss of the first nucleotide (G₋₁) in tRNAHis converts it to a substrate for MST1 with a Km value (0.7 μM) comparable to that of Formula (0.3 μM), and addition of G₋₁ to Formula allows efficient histidylation by histidyl-tRNA synthetase. We also show that MST1 from Candida albicans, a yeast in which CUN codons remain assigned to leucine, could not threonylate Formula , suggesting that MST1 has coevolved with Formula . Our work provides the first clear example of a recent recoding event caused by alloacceptor tRNA gene recruitment.
Agid:
2322522