New publication by the Carell lab on Selective Chemical Manipulation of Mannosyl- and Galactosyl-Queuosine in tRNAs of Living Cells
Pichler A, Peev E, Ge Q, Ben Helal G, Heiss M, Xefteris S, Müller M, Carell T (2025) Selective Chemical Manipulation of Mannosyl- and Galactosyl-Queuosine in tRNAs of Living Cells.Angew Chem Int Ed Engl, e202508499 Link
Abstract:
Queuosine is a hypermodified nucleoside found in the anticodon loop of tRNAs decoding the amino acids His, Asn, Tyr, and Asp. In tRNATyr, the homoallylic 2-hydroxyl group of the cyclopentene ring carries an additional β-galactose, while in tRNAAsp, an α-mannose is connected to the allylic 3-hydroxyl group. Although these additional sugar modifications were found in the tRNAs of many animals, including humans, their purpose remains unknown. Recently, the Q-tRNA galatosyl- and mannosyltransferase (QTGAL and QTMAN) that attach the galactose and mannose moieties to the different OH groups of the Q-base have been identified, but the function of this transfer reaction remains unclear. Here, we performed feeding experiments with synthetic deoxyqueuine derivatives that lack either the allylic, the homoallylic, or both hydroxyl groups. Analysis of the queuosine derivatives that are found in the corresponding tRNAs shows that the glycosylases attach the sugar with precise specificity, suggesting decisive functions of the galactose and mannose sugar moieties in the decoding process.
Read the full paper here: https://onlinelibrary.wiley.com/doi/10.1002/anie.202508499
