QTRT1 encodes the catalytic subunit of the eukaryotic tRNA guanine transglycosylase complex that modifies specific tRNAs by replacing guanine with queuosine at position 34 of the anticodon wobble position 1. This enzyme forms a heterodimeric complex with the non-catalytic QTRT2 subunit and targets tRNAs with GUN anticodons (tRNA-Asp, -Asn, -His, and -Tyr) 12. The queuosine modification requires queuine, a micronutrient derived from diet or gut microbiome, making this a microbiome-dependent tRNA modification 32. Functionally, QTRT1-mediated queuosine modification regulates translation efficiency and affects cellular processes including proliferation, tight junction formation, and immune responses 345. The modification occurs on precursor tRNAs before splicing, demonstrating coordinated tRNA processing 6. QTRT1 deficiency is associated with inflammatory bowel disease, where reduced expression correlates with altered epithelial barrier function and decreased cell proliferation 4. In cancer contexts, QTRT1 affects tumor growth and microbiome recruitment, with knockout cells showing altered proliferation and migration properties 3. The enzyme also influences MHC-II expression in dendritic cells, suggesting roles in immune function 5.