Fungi of the order Mucorales express a "sealing-only" tRNA ligase.
TRL1
antifungal target
tRNA splicing
Journal
bioRxiv : the preprint server for biology
Titre abrégé: bioRxiv
Pays: United States
ID NLM: 101680187
Informations de publication
Date de publication:
17 Nov 2023
17 Nov 2023
Historique:
pubmed:
28
11
2023
medline:
28
11
2023
entrez:
28
11
2023
Statut:
epublish
Résumé
Some eukaryotic pre-tRNAs contain an intron that is removed by a dedicated set of enzymes. Intron-containing pre-tRNAs are cleaved by tRNA splicing endonuclease (TSEN), followed by ligation of the two exons and release of the intron. Fungi use a "heal and seal" pathway that requires three distinct catalytic domains of the tRNA ligase enzyme, Trl1. In contrast, humans use a "direct ligation" pathway carried out by RTCB, an enzyme completely unrelated to Trl1. Because of these mechanistic differences, Trl1 has been proposed as a promising drug target for fungal infections. To validate Trl1 as a broad-spectrum drug target, we show that fungi from three different phyla contain Trl1 orthologs with all three domains. This includes the major invasive human fungal pathogens, and these proteins each can functionally replace yeast Trl1. In contrast, species from the order Mucorales, including the pathogens
Identifiants
pubmed: 38014270
doi: 10.1101/2023.11.16.567474
pmc: PMC10680797
pii:
doi:
Types de publication
Preprint
Langues
eng
Subventions
Organisme : NIGMS NIH HHS
ID : R35 GM141710
Pays : United States
Commentaires et corrections
Type : UpdateIn
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