Why tRNAs are Different

Abstract

tRNA sequences differ substantially from one another and each tRNA contains a unique set of posttranscriptional modifications. We propose that an important selective pressure that leads to this structural diversity is that each aminoacyl-tRNA must interact with the translational machinery with equivalent kinetic and thermodynamic properties. In other words, each tRNA body has evolved to compensate for the differing contributions of the esterified amino acids and the anticodon that are unique to each tRNA. In the case of the complex formed between aminoacyl-tRNA and EF-Tu, site directed mutagenesis of both the protein and the tRNA reveal certain locations in the interface where the affinity is adjusted depending upon the identity of the esterified amino acid. As a result, the sequence diversity among the acceptor and T stems of tRNAs has primarily evolved to adjust the EF-Tu binding affinity. Similarly, mutations in the anticodon stem-loop of tRNAs show that this part of the molecule is important for adjusting the affinity of the codon-anticodon interaction to that tRNAs bind ribosomes and progress through the translational mechanism uniformly.