Molecular architectures and mechanisms of RNA-modifying ribozymes

A large number of natural RNA modifications expand the structural and functional diversity of RNA. Methylated nucleotides represent an important class of RNA modifications, that are installed by methyltransferase enzymes and have important physiological roles. The diversity of cellular RNA functions demands new tools for studying RNA localization, folding and structural dynamics. Ribozymes have emerged as powerful tools for modifying RNA in vitro and in cells. This presentation will discuss the recently discovered methyltransferase ribozyme MTR1 that generates 1-methyl-adenosine in the target RNA[1] and the SAM-analogue utilizing ribozyme SAMURI.[2]

We will focus on how such ribozymes are discovered by in vitro selection and discuss their crystal structures and molecular mechanisms. These fundamental insights allow us to engineer the ribozymes for various RNA targets, such that ribozymes can be envisioned for modulating the native RNA modification landscape and for installing synthetic post-transcriptional RNA modifications for RNA labelling and visualization.

References:

[1] a) C.P.M. Scheitl, M. GhaemMaghami, A.K. Lenz, C. Höbartner. Nature 2020, 587, 663-667. b). C.P.M. Scheitl M. Mieczkowski, H. Schindelin, C. Höbartner. Nat Chem Biol 2022, 18, 547-555.

[2] T. Okuda, A.K. Lenz, F. Seitz, J. Vogel, C. Höbartner. Nat. Chem. 2023, 15, 1523-1531.