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Nucleic Acids Research, 2003, Vol. 31, No. 22 6383-6391
© 2003 Oxford University Press

Article

Roles of 5-substituents of tRNA wobble uridines in the recognition of purine-ending codons

Kazuyuki Takai*,1,2,3 and Shigeyuki Yokoyama4,5,6

1 Cell-Free Science and Technology Research Center, 2 Department of Applied Chemistry, Faculty of Engineering and 3 Venture Business Laboratory, Ehime University, 3, Bunkyo-cho, Matsuyama, Ehime 790-8577, Japan and 4 Department of Biophysics and Biochemistry, School of Science, University of Tokyo, 3-7-1, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan, 5 Protein Research Group, RIKEN Genomic Sciences Center, 1-7-22 Suehiro-cho, Tsurumi, Yokohama 230-0045, Japan and 6 Cellular Signaling Laboratory and Structurome Research Group, RIKEN Harima Institute at Spring-8, 1-1-1 Kohto, Mikazuki-cho, Sayo, Hyogo 679-5148, Japan

*To whom correspondence should be addressed at Cell-free Science and Technology Research Center, Ehime University, 3, Bunkyo-cho, Matsuyama, Ehime 790-8577, Japan. Tel/Fax: +81 89 927 9925; Email: takai{at}eng.ehime-u.ac.jp

Many tRNA molecules that recognize the purine-ending codons but not the pyrimidine-ending codons have a modified uridine at the wobble position, in which a methylene carbon is attached directly to position 5 of the uracil ring. Although several models have been proposed concerning the mechanism by which the 5-substituents regulate codon-reading properties of the tRNAs, none could explain recent results of the experiments utilizing well-characterized modification-deficient strains of Escherichia coli. Here, we first summarize previous studies on the codon-reading properties of tRNA molecules with a U derivative at the wobble position. Then, we propose a hypothetical mechanism of the reading of the G-ending codons by such tRNA molecules that could explain the experimental results. The hypothesis supposes unconventional base pairs between a protonated form of the modified uridines and the G at the third position of the codon stabilized by two direct hydrogen bonds between the bases. The hypothesis also addresses differences between the prokaryotic and eukaryotic decoding systems.


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