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: |
Guanine
AcademicSubjects/SCI00010 Queuosine Wobble base pair Biology Substrate Specificity Nucleobase 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Animal model Chemical Biology and Nucleic Acid Chemistry RNA Transfer Genetics Humans Pentosyltransferases 030304 developmental biology chemistry.chemical_classification 0303 health sciences RNA Enzyme chemistry Biochemistry 030220 oncology & carcinogenesis Transfer RNA |
| 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 |
| Externí odkaz: |
|