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Mol Cell Biol. 2008 May;28(10):3301-12. doi: 10.1128/MCB.01542-07. Epub 2008 Mar 10.

Eukaryotic wobble uridine modifications promote a functionally redundant decoding system.

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Department of Molecular Biology, Umeå University, 901 87 Umeå, Sweden.


The translational decoding properties of tRNAs are modulated by naturally occurring modifications of their nucleosides. Uridines located at the wobble position (nucleoside 34 [U(34)]) in eukaryotic cytoplasmic tRNAs often harbor a 5-methoxycarbonylmethyl (mcm(5)) or a 5-carbamoylmethyl (ncm(5)) side chain and sometimes an additional 2-thio (s(2)) or 2'-O-methyl group. Although a variety of models explaining the role of these modifications have been put forth, their in vivo functions have not been defined. In this study, we utilized recently characterized modification-deficient Saccharomyces cerevisiae cells to test the wobble rules in vivo. We show that mcm(5) and ncm(5) side chains promote decoding of G-ending codons and that concurrent mcm(5) and s(2) groups improve reading of both A- and G-ending codons. Moreover, the observation that the mcm(5)U(34)- and some ncm(5)U(34)-containing tRNAs efficiently read G-ending codons challenges the notion that eukaryotes do not use U-G wobbling.

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