engleski

Keeping translation canonical: Lessons from aminoacyl-tRNA synthetases

Compromised fidelity of protein synthesis may disrupt protein function and homeostasis and lead to impaired cell viability and growth. We focus on the accuracy of aminoacylation – the reaction by which amino acids are covalently coupled to their cognate tRNAs for delivery to the ribosome. This reaction, that translates the genetic code, is catalyzed by aminoacyl-tRNA synthetases (AARSs). What is the weakest link in keeping aminoacylation accurate? And how do AARSs control this link? Traditionally, the main threats for the accuracy of aminoacylation were sought among twenty canonical proteinogenic amino acids. We showed, however, that the editing domains of isoleucyl-, valyl-, and leucyl-tRNA synthetases (IleRS, ValRS, LeuRS) are highly efficient in preventing non- canonical amino acids, like norvaline and alpha- aminobutyrate, from participating in translation (Previously published in: Bilus et al. (2019) J Mol Biol. 431, 1284-1297 and Zivkovic et al (2020) FEBS J. 287, 800-813). We further demonstrated that incorporation of norvaline to Escherichia coli’s proteome at isoleucine positions promotes higher toxicity than the same level of incorporation of valine. Taking into account that norvaline and alpha-aminobutyrate were likely abundant in abiotic conditions, and the common evolutionary origin of IleRS, ValRS and LeuRS, an intriguing hypothesis, that the editing domain was acquired by the ILVRS ancestor to ensure participation of only twenty canonical amino acids in modern translation, will be discussed.

aminoacyl-tRNA synthetases, editing, translational accuracy, non-proteinogenic amino acids

nije evidentirano