Qtrt1, queuine tRNA-ribosyltransferase 1, is a key catalytic subunit of the eukaryotic tRNA-guanine transglycosylase complex, along with QTRT2. It facilitates the queuosinylation of specific tRNAs, a process where queuine, obtained from the gut microbiota, is introduced into tRNA. This modification is crucial for ensuring the fidelity and efficiency of translation from RNA to protein, and thus plays an important role in various biological processes [1,2,3,4,5,6].

Qtrt1 knockout mouse models have provided significant insights. Loss of Q-tRNA due to Qtrt1 knockout leads to learning and memory deficits. Ribo-Seq analysis in the hippocampus of these mice showed ribosome stalling on Q-decoded codons and an imbalance in translation elongation speed between codons with weak and strong anticodon interactions. Female mice were more severely affected than males, and proteomics analysis confirmed deregulation of synaptogenesis and neuronal morphology [1]. In addition, Qtrt1 deficiency in human breast cancer cells could change the functions of regulation genes related to cell proliferation, tight junction formation, and migration both in vitro and in a breast tumor mouse model in vivo. It also altered the recruitment of core bacteria in tumors [4]. In IBD, QTRT1 expression was significantly downregulated in patients, and in Qtrt1 knockout mice, reduced QTRT1 was associated with changes in cell proliferation and intestinal junctions [2].

In conclusion, Qtrt1 is essential for tRNA queuosine modification, which impacts translation and is involved in multiple biological processes. The use of Qtrt1 knockout mouse models has revealed its role in cognitive function, breast cancer development, and intestinal inflammation, providing valuable insights into the molecular mechanisms underlying these processes and potential therapeutic targets for related diseases.