Synthesis of galactosyl-queuosine and distribution of hypermodified Q-nucleosides in mouse tissues.

Queuosine (Q) is a hypermodified RNA nucleoside that is found in tRNA His , tRNA Asn , tRNA Tyr , and tRNA Asp . It is located at the wobble position of the tRNA anticodon loop, where it can interact both with U or C bases located at the respective position of the corresponding mRNA codons. In higher eukaryotes, including humans, the Q base is for yet unknown reasons further modified in tRNA Tyr and tRNA Asp by the addition of a galactose or mannose sugar, respectively. The reason for this additional modification, and how the sugar modification is orchestrated with Q-formation and insertion, is unknown. Here, we report a total synthesis of the hypermodified nucleoside galactosyl-queuosine (galQ). The availability of the compound enabled us to study the absolute levels of the Q-family nucleosides in six different organs of new-born and adult mice, and also in human cytosolic tRNA. Our synthesis now paves the way to a more detailed analysis of the biological function of the Q-nucleoside family.