tRNA with GUN anticodons (GUN-tRNAs)

The tRNA with GUN anticodons (comprising tRNA-Asn, tRNA-Asp, tRNA-His, and tRNA-Tyr) is a specialized subset of transfer RNAs characterized by a guanine at the wobble position (G34) and a uracil at position 35. These tRNAs are the exclusive substrates for the enzyme tRNA-guanine transglycosylase (TGT), which replaces the wobble guanine with the hypermodified base queuosine (Q), a nutrient-derived micronutrient. This modification is essential for the precise regulation of protein synthesis, as it modulates the decoding efficiency and accuracy of codons ending in U or C, thereby maintaining proteome stability. In various pathological conditions, particularly in aggressive cancers and certain neurological disorders like Multiple Sclerosis, these tRNAs are frequently hypomodified, leading to translational errors and disease progression. Therapeutic interventions targeting this system focus on restoring queuosine levels through supplementation or modulating TGT activity, making these tRNAs a key target for addressing translational dysregulation in precision medicine.

Other names

tRNA with GU anticodonsQueuosine-modified tRNAsGUN-tRNAstRNA-Asn/Asp/His/Tyr group

Restoration or modulation of queuosine (Q) modification at the wobble position (G34) to regulate translational speed and accuracy.