queuosine

Queuosine is a modified nucleoside found in transfer RNA (tRNA). It is a complex, guanine-derived base incorporated at the wobble position (34) of certain cytoplasmic tRNAs, replacing the usual guanine. In many bacteria and in a broad range of eukaryotes, queuosine occurs in the tRNAs for aspartic acid (tRNA Asp), asparagine (tRNA Asn), histidine (tRNA His), and tyrosine (tRNA Tyr). The presence of queuosine in these anticodons influences codon recognition and translation.

Biogenesis and incorporation: In bacteria, queuosine is synthesized de novo through a dedicated biosynthetic pathway, producing a queuosine reparative precursor that is ultimately inserted into tRNA by tRNA-guanine transglycosylase (TGT). TGT replaces the guanine at position 34 with the queuine base, yielding the mature, queuosine-containing tRNA. In eukaryotes, queuosine is not produced de novo; cells salvage queuine from dietary sources or from the gut microbiota and incorporate it into tRNA via the same TGT enzyme system.

Function and significance: The queuosine modification at the wobble position modulates codon-anticodon interactions, affecting translation efficiency and fidelity. It is thought to influence decoding accuracy and may play a role in cellular responses to nutrient status and stress. Queuosine levels can be influenced by diet and the microbiome, reflecting a link between metabolism, nutrition, and gene expression.

Clinical and biological notes: Queuosine is one example of tRNA hypermodifications that differ between organisms and can reflect metabolic state. Its study sheds light on how cellular nutrition status can impact protein synthesis.