Queuine tRNA-ribosyltransferase catalytic subunit 1 (QTRT1)

Queuine tRNA-ribosyltransferase catalytic subunit 1 (QTRT1) is the catalytic core of the eukaryotic tRNA-guanine transglycosylase (TGT) enzyme complex responsible for post-transcriptional modification of select tRNAs. It catalyzes the exchange of guanine for queuine at the wobble position (position 34) of tRNAs for asparagine, aspartic acid, histidine, and tyrosine. This structural modification of tRNA is essential for proper decoding during translation and influences protein synthesis fidelity, cell signaling, and cellular growth pathways. QTRT1 requires heterodimerization with QTRTD1 for full activity. The protein is expressed in the cytoplasm and mitochondria, and its levels and activity are altered in certain cancers, impacting cell proliferation, migration, and junctional integrity. Aberrant queuine modification resulting from QTRT1 deficiency or dysregulation has been linked to tumorigenesis, neurodegeneration, microbiome-mediated physiology, and inflammation. Eukaryotes cannot synthesize queuine and must acquire it from diet and microbiota. Structural studies reveal a central (β/α)8 barrel and zinc-binding domain critical for its catalytic activity. No clinically approved drugs directly target QTRT1, but its functional and disease relevance make it a subject of ongoing research for biomarker and therapeutic development.

Other names

Queuine tRNA-ribosyltransferase catalytic subunit 1QTRT1TGTTGUTGuanine insertion enzymetRNA-guanine transglycosylaseFP323543-KD subunitQueuine tRNA-ribosyltransferase 1Catalytic subunitQueuine insertion enzymetRNA-guanine transglycosylase catalytic subunit 1

Hypothetical mechanisms include inhibition of enzymatic activity to perturb tRNA queuosine modification, thereby influencing translational fidelity and cell proliferation. No clinically validated drugs or inhibitors have been described