Surprising Contribution to Aminoacylation and Translation of Non-Watson: Crick Pairs in tRNA

• Published in: Proceedings of the National Academy of Sciences - PNAS 2006-03, Vol.103 (12), p.4570-4575
• Main Author: McClain, William H.
• Format: Article
• Language: English
• Subjects: Amino acids; Anticodon; Bacteria; Base Pair Mismatch; Base Sequence; Bioinformatics; Biological Sciences; Computational Biology; Datasets; Escherichia coli; Evolution; Gels; Genetic mutation; Genetics; Genomics; Molecular Sequence Data; Molecules; Mutation; Nucleic Acid Conformation; Opal; Physical Sciences; Plasmids; Protein Biosynthesis - genetics; Ribonucleic acid; Ribosomal DNA; Ribosomes - metabolism; RNA; RNA, Transfer, Gly - genetics; RNA, Transfer, Gly - metabolism; Transfer RNA; Transfer RNA Aminoacylation
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0600592103

Molecules of transfer RNA (tRNA) typically contain four stems composed of Watson-Crick (W-C) base pairs and infrequent mispairs such as G-U and A-C. The latter mispairs are fundamental units of RNA secondary structure found in nearly every class of RNA and are nearly isomorphic to W-C pairs. Therefore, they often substitute for G-C or A-U base pairs. The mispairs also have unique chemical, structural, and dynamic conformational properties, which can only be partially mimicked by W-C base pairs. Here, I characterize the identities and tasks of six mutant G-U and A-C mispairs in Escherichia coli$tRNA^{Gly}$using genetic and bioinformatic tools and show that mispairs are significantly more important for aminoacylation and translation than previously realized. Mispairs boost aminoacylation and translation primarily because they activate tRNA by means of their conformational flexibility. The statistical preservation of the six mutant mispair sites across$tRNA^{Gly}$in many organisms points to a fundamental structure-function signature within$tRNA^{Gly}$with possible analogous missions in other RNAs.