Biogenesis and roles of tRNA queuosine modification and its glycosylated derivatives in human health and diseases

Abstract

Various types of post-transcriptional modifications contribute to physiological functions by regulating the abundance and function of RNAs. In particular, tRNAs have the widest variety and largest number of modifications, with crucial roles in protein synthesis. Queuosine (Q) is a characteristic tRNA modification with a 7-deazaguanosine core structure bearing a bulky side chain with a cyclopentene group. Q and its derivatives are found in the anticodon of specific tRNAs in both bacteria and eukaryotes. In metazoan tRNAs, Q is further glycosylated with galactose or mannose. The functions of these glycosylated Qs remained unknown for nearly half a century since their discovery. Recently, our group identified the glycosyltransferases responsible for these tRNA modifications and elucidated their biological roles. We, here, review the biochemical and physiological functions of Q and its glycosylated derivatives as well as their associations with human diseases, including cancer and inflammatory and neurological diseases.

Keywords: Proteostasis; QTGAL; QTMAN; QTRT1; QTRT2; galactosyl queuosine; glycosylated queuosine; mannosyl queuosine; optimal translation; queuosine; tRNA modification; tRNA modopahy.