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

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.

F. Seitz, T. Jungnickel, N. Kleiber, J. Kretschmer, J. Adelmann, J. Dietzsch, K.E. Bohnsack, M.T. Bohnsack, C. Höbartner
Atomic mutagenesis of N⁶-methyladenosine reveals distinct recognition modes of human m⁶A reader and eraser proteins
J. Am. Chem. Soc. 2024, 146, 11, 7803–7810

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.