Ribozymes for RNA‐Catalyzed RNA Methylation and Labeling

RNA is a cornerstone of life, executing diverse essential functions. A key determinant of RNA's functional versatility lies in natural nucleoside modifications, which greatly expand the chemical diversity and are vital for regulating the stability, folding, and function of RNA structures involved in cellular processes. Artificially introduced RNA modifications such as reactive handles, affinity tags or fluorescent reporters, are key to enable RNA isolation, imaging and tracking, in order to unravel the important regulatory roles of RNAs in any organism. Covalent RNA labeling methods are particularly desirable for downstream applications. RNA catalysts, so-called ribozymes, have gained increasing attention as tools for the site-directed installation of various functionalities, such as clickable tags, fluorophores, or methyl groups. Thereby, ribozymes can create both, artificially as well as naturally modified RNAs of interest. This review provides a collection of currently available ribozymes for the covalent modification of RNA that were obtained by in vitro selection using suitable cofactors. We discuss self-modifying catalysts for RNA tagging and fluorescent labeling, as well as ribozymes for RNA-modification in an intermolecular setup. Finally, we introduce the growing collection of methyltransferase ribozymes for site-specific installation of natural methylated nucleosides and provide an outlook on open questions and future developments of the research field.