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

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.