The human tRNA-guanine transglycosylase displays promiscuous nucleobase preference but strict tRNA specificity

Autor: Franciane Chevot, Claire Fergus, Mathias O. Senge, John M. Southern, Stephen J. Connon, Mashael A. Alqasem, Vincent P. Kelly, Emiliano Sorrentino, Ciara McDonnell, Michelle Cotter, Karsten Hokamp
Rok vydání: 2021
Předmět:
Zdroj: Nucleic Acids Research
ISSN: 1362-4962
0305-1048
DOI: 10.1093/nar/gkab289
Popis: Base-modification can occur throughout a transfer RNA molecule; however, elaboration is particularly prevalent at position 34 of the anticodon loop (the wobble position), where it functions to influence protein translation. Previously, we demonstrated that the queuosine modification at position 34 can be substituted with an artificial analogue via the queuine tRNA ribosyltransferase enzyme to induce disease recovery in an animal model of multiple sclerosis. Here, we demonstrate that the human enzyme can recognize a very broad range of artificial 7-deazaguanine derivatives for transfer RNA incorporation. By contrast, the enzyme displays strict specificity for transfer RNA species decoding the dual synonymous NAU/C codons, determined using a novel enzyme-RNA capture-release method. Our data highlight the broad scope and therapeutic potential of exploiting the queuosine incorporation pathway to intentionally engineer chemical diversity into the transfer RNA anticodon.
Databáze: OpenAIRE