Synthesis of Galactosyl-Queuosine and Distribution of Hypermodified Q-Nucleosides in Mouse Tissues

Thumbs, Peter; Ensfelder, Timm T.; Hillmeier, Markus; Wagner, Mirko; Heiss, Matthias; Scheel, Constanze; Schön, Alexander; Müller, Markus; Michalakis, Stylianos; Kellner, Stefanie und Carell, Thomas (11. März 2020): Synthesis of Galactosyl-Queuosine and Distribution of Hypermodified Q-Nucleosides in Mouse Tissues. In: Angewandte Chemie International Edition

Abstract

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 with U as well as C bases located at the respective position of the corresponding mRNA codons. In tRNA-Tyr and tRNA-Asp of higher eukaryotes, including humans, the Q base is for yet unknown reasons further modified by the addition of a galactose and a 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 newborn 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.

• Dokumententyp: Zeitschriftenartikel
• EU Funded Grant Agreement Number: 741912
• EU-Projekte: Horizon 2020 > ERC Grants > ERC Advanced Grant > ERC Grant 741912: EPiR - The Chemical Basis of RNA Epigenetics
• Publikationsform: Publisher's Version
• Keywords: galactosylation; mannosylation; mannosyl-queuosine; queuosine; RNA modifications
• Fakultät: Chemie und Pharmazie > Department Chemie
• Themengebiete: 500 Naturwissenschaften und Mathematik > 540 Chemie
• ISSN: 1521-3773
• Sprache: Englisch

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