Wobble transfer RNA modifications optimize dynamic proteome expression
In this study published by Pierre Close (WELBIO ULiège) and Francesca Rapino, the team set out to investigate the mechanisms underlying the reprogramming of protein synthesis through the regulation of tRNAs. The synthesis of new proteins is a highly regulated process that is responsible for the expression of all the proteins present in a cell, in a given context. During protein synthesis, messenger RNAs (mRNAs) are translated into proteins, via adaptor molecules, tRNAs which, within the ribosomes, ensure recognition of the codon sequence of mRNAs and add the corresponding amino acid to the nascent peptide chain. In order to ensure optimal translation and protein synthesis under the best conditions, the tRNAs are modified at their anticodon. In particular, the modifications at their wobble base, including uridine (U34-tRNA), enable perfect fidelity in the translation of mRNAs by tRNAs.
This work shows that a large majority of genes are insensitive to U34-tRNA modifications. On the other hand, for a certain number of genes, these modifications are essential during their translation, otherwise, the proteins produced are unstable and are degraded. These results pave the way for a more systematic prediction of the identity of proteins for which expression depends on the regulation of the numerous modifications of tRNAs.