Site-specific RNA methylation by a methyltransferase ribozyme
Please always quote using this URN: urn:nbn:de:bvb:20-opus-218687
- Nearly all classes of coding and non-coding RNA undergo post-transcriptional modification including RNA methylation. Methylated nucleotides belong to the evolutionarily most conserved features of tRNA and rRNA.1,2 Many contemporary methyltransferases use the universal cofactor S-adenosylmethionine (SAM) as methyl group donor. This and other nucleotide-derived cofactors are considered as evolutionary leftovers from an RNA World, in which ribozymes may have catalysed essential metabolic reactions beyond self-replication.3 Chemically diverseNearly all classes of coding and non-coding RNA undergo post-transcriptional modification including RNA methylation. Methylated nucleotides belong to the evolutionarily most conserved features of tRNA and rRNA.1,2 Many contemporary methyltransferases use the universal cofactor S-adenosylmethionine (SAM) as methyl group donor. This and other nucleotide-derived cofactors are considered as evolutionary leftovers from an RNA World, in which ribozymes may have catalysed essential metabolic reactions beyond self-replication.3 Chemically diverse ribozymes seem to have been lost in Nature, but may be reconstructed in the laboratory by in vitro selection. Here, we report a methyltransferase ribozyme that catalyses the site-specific installation of 1-methyladenosine (m1A) in a substrate RNA, utilizing O6-methylguanine (m6G) as a small-molecule cofactor. The ribozyme shows a broad RNA sequence scope, as exemplified by site-specific adenosine methylation in tRNAs. This finding provides fundamental insights into RNA’s catalytic abilities, serves a synthetic tool to install m1A in RNA, and may pave the way to in vitro evolution of other methyltransferase and demethylase ribozymes.…
Author: | Carolin P.M. Scheitl, Mohammad Ghaem Maghami, Ann-Kathrin Lenz, Claudia HöbartnerORCiD |
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URN: | urn:nbn:de:bvb:20-opus-218687 |
Document Type: | Preprint |
Faculties: | Fakultät für Chemie und Pharmazie / Institut für Organische Chemie |
Language: | English |
Parent Title (English): | Nature |
Year of Completion: | 2020 |
Source: | Nature (2020) volume 587, pages 663–667. https://doi.org/10.1038/s41586-020-2854-z |
DOI: | https://doi.org/10.1038/s41586-020-2854-z |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 54 Chemie / 547 Organische Chemie |
Tag: | Methyltransferase Ribozyme; RNA Enzymes; position-specific installation of m1A in RNA |
Release Date: | 2020/12/18 |
EU-Project number / Contract (GA) number: | 682586 |
OpenAIRE: | OpenAIRE |
Licence (German): | Deutsches Urheberrecht |