Fungi of the Order Mucorales Express a “Sealing-Only” tRNA Ligase

Authors

Khondakar Sayef Ahammed
Ambro van Hoof

Publication Date

3-18-2024

Journal

RNA

Abstract

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, 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 can each functionally replace yeast Trl1. In contrast, species from the order Mucorales, including the pathogens

Keywords

Humans, RNA Ligase (ATP), Saccharomyces cerevisiae, RNA, Transfer, Saccharomyces cerevisiae Proteins, RNA Precursors, RNA Splicing, Mucorales

DOI

10.1261/rna.079957.124

PMID

38307611

PMCID

PMC10946435

PubMedCentral® Posted Date

4-1-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes