PreQ

PreQ is a term used for intermediates in the biosynthesis of queuosine, a hypermodified nucleoside found in the wobble position of certain tRNAs. The designation covers two related compounds: preQ0, 7-cyano-7-deazaguanine, and preQ1, 7-aminomethyl-7-deazaguanine. These molecules share the deazaguanine core, differing in the substituent at the seventh position.

Biological context: Queuosine replaces guanine at position 34 in many tRNAs and is believed to influence decoding properties. In bacteria, queuosine is synthesized de novo via a pathway that converts GTP through preQ0 and preQ1 to the final queuosine-containing nucleoside. Early steps involve enzymes such as QueC, QueD, and QueE to form preQ0, followed by QueF-mediated reduction to preQ1. The preQ1 moiety is then incorporated into tRNA by tRNA-guanine transglycosylase (TGT), with subsequent processing by enzymes such as QueA and QueG to yield mature queuosine.

In contrast, many eukaryotes rely on salvage of queuine, the free base corresponding to queuosine, from dietary sources or gut microbiota. TGT can incorporate queuine into tRNA, rather than proceeding through the full de novo preQ biosynthetic steps inside the cell.

Function and significance: Queuosine-containing tRNAs are associated with translational efficiency and accuracy and may participate in cellular responses to metabolic status and stress. The availability of preQ intermediates or queuine can influence protein synthesis in organisms that harbor Q in their tRNAs.