Native RNA modifications

In collaboration with Markus Bohnsack, Uni Göttingen we study methyl transferase enzymes (e.g. METTL16, NSUN3) and elucidate interconnected modification patterns as well as structural and functional consequences of human tRNA modifications.

N. Kleiber, N. Lemus-Diaz, C. Stiller, M. Heinrichs, M. Mong-Quyen Mai, P. Hackert, R. Richter-Dennerlein, C. Höbartner, K. E. Bohnsack, M. T. Bohnsack
The RNA methyltransferase METTL8 installs m³C₃₂ in mitochondrial tRNAs^Thr/Ser(UCN) to optimise tRNA structure and mitochondrial translation
Nat. Commun. 2022, 13, 209. First published 11 January 2022.

S. Haag, K.E. Sloan, N. Ranjan, A.S. Warda, J. Kretschmer, C. Blessing, B. Hübner, J. Seikowski, S. Dennerlein, P. Rehling, M.V. Rodnina, C. Höbartner, M.T. Bohnsack,
NSUN3 and ABH1 modify the wobble position of mt-tRNAMet to expand codon recognition in mitochondrial translation
EMBO Journal  2016, 35, 2104-2119.

Chemical synthesis of phosphoramidite building blocks and their use in solid-phase RNA synthesis lays the groundwork for the elucidation of biochemical pathways, structural consequences and cellular functions of RNA modifications, in health and disease.

Examples of recently synthesized phosphoramidites:

m3C: A. Liaqat, M.V. Sednev, C. Stiller, C. Höbartner
RNA-cleaving deoxyribozymes differentiate methylated cytidine isomers in RNA
Angew. Chem. Int. Ed. 2021, 60, 19058–19062.

ms2i6A: N. Kleiber, N. Lemus-Diaz, C. Stiller, M. Heinrichs, M. Mong-Quyen Mai, P. Hackert, R. Richter-Dennerlein, C. Höbartner, K. E. Bohnsack, M. T. Bohnsack
The RNA methyltransferase METTL8 installs m³C₃₂ in mitochondrial tRNAs^Thr/Ser(UCN) to optimise tRNA structure and mitochondrial translation
Nat. Commun. 2022, 13, 209.