Biogenesis and Evolution of Functional tRNAs

Faithful translation of genomes into proteomes depends, mainly, on the activity of transfer RNA (tRNA) as universal adaptor, as insightfully predicted by Crick. The central role of this relatively simple oligonucleotide depends upon a very large number of intermolecular interactions, some of which require that tRNAs maintain a constant general structure, while others depend on specific features that discriminate any given tRNA from the rest. Posttranscriptional modifications that increase the chemical diversity contained in the nucleotides of tRNAs can serve both purposes. Chemical modifications of tRNAs, thus, come in two general flavors: those that help to maintain the general shape of the molecule, and those that improve its interactions with one or more of its many molecular partners. Although the function of most of the chemical modifications known to occur in tRNAs remain unknown, up-to-date knowledge allows us to analyze the majority of them in some model organisms, including Saccharomyces cerevisiae. Here we will review our current understanding on the function of tRNA modifications, generally dividing them into two families: those that are likely to influence the structure of tRNA, and those that may play a role in the codon-anticodon interaction at the decoding center of the ribosome.