![]() ![]() ![]() Crick offered the idea that uridine (U) at the first position of the anticodon, position 34 in tRNA ( Fig. 2), would base pair with guanosine (G) and that inosine (I), which at the time had only recently been found at position 34 in yeast tRNA Ala, 2 would base pair with uridine, cytidine (C) and adenosine (A). 1 At the time there was evidence to suggest that the first two positions, N1N2, of mRNA's 3-nucleoside codons were uniquely identified by the tRNA with some ambiguity in the third position. Fifty years ago, Francis Crick published the Wobble Hypothesis. ![]() denotes canonical Watson-Crick hydrogen bonding, does not explain how the 61 amino acid codons are decoded by far fewer tRNAs.Complementariness of base pairing between tRNA's anticodon and the mRNA codon, A Three codons are recognized by protein factors and correspond to translation termination signals. Sixty-one of 64 3-nucleoside codons of the mRNA, N1N2N3, are decoded in frame with a complementary sequence of the tRNA anticodon, N 34N 35N 36. Translation of the Universal Genetic Code ( Fig. 1) into the amino acid sequence of proteins requires accurate and efficient decoding of mRNA (mRNA) on the ribosome by tRNA (tRNA). Understanding natural modifications has inspired evolutionary insights and possible innovation in protein synthesis. Here, we review tRNA wobble codon recognition using specific examples of simple and complex modification chemistries that alter tRNA function. As forecast by the Modified Wobble Hypothesis 25 years ago, some individual modifications at tRNA's wobble position have evolved to restrict codon recognition whereas others expand the tRNA's ability to read as many as four synonymous codons. Their contribution with regards to chemistry, structure and dynamics reveal individual and combined effects on tRNA function in recognition of cognate and wobble codons. The post-transcriptional modifications of tRNA's anticodon domain are the most diverse and chemically complex of any RNA modifications. Many more naturally-occurring modifications have been elucidated and continue to be discovered. A simple post-transcriptional modification of tRNA, deamination of adenosine to inosine at the first, or wobble, position of the anticodon, inspired Francis Crick's Wobble Hypothesis 50 years ago. ![]()
0 Comments
Leave a Reply. |