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

  • Angew Chem Int Ed Engl. 2020 Jul 20;59(30):12352-12356. doi: 10.1002/anie.202002295.
Peter Thumbs  1 ,  Timm T Ensfelder  1 ,  Markus Hillmeier  1 ,  Mirko Wagner  1 ,  Matthias Heiss  1 ,  Constanze Scheel  2 ,  Alexander Schön  1 ,  Markus Müller  1 ,  Stylianos Michalakis  2  3 ,  Stefanie Kellner  1 ,  Thomas Carell  1
Affiliations
  • 1. Department of Chemistry, Ludwig-Maximilians-Universität München, Butenandtstr. 5-13, 81377, Munich, Germany.
  • 2. Department of Pharmacy, Ludwig-Maximilians-Universität München, Butenandtstr. 5-13, 81377, Munich, Germany.
  • 3. Department of Ophthalmology, Ludwig-Maximilians-Universität München, Mathildenstr. 8, 80336, Munich, Germany.
PMID: 32160400 DOI: 10.1002/anie.202002295
Abstract

Queuosine (Q) is a hypermodified RNA nucleoside that is found in tRNAHis , tRNAAsn , tRNATyr , and tRNAAsp . 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 tRNATyr and tRNAAsp 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.

Keywords
RNA modifications; galactosylation; mannosyl-queuosine; mannosylation; queuosine.