RNA-Cleaving Deoxyribozymes Differentiate Methylated Cytidine Isomers in RNA
Zitieren Sie bitte immer diese URN: urn:nbn:de:bvb:20-opus-254544
- Deoxyribozymes are emerging as modification-specific endonucleases for the analysis of epigenetic RNA modifications. Here, we report RNA-cleaving deoxyribozymes that differentially respond to the presence of natural methylated cytidines, 3-methylcytidine (m\(^3\)C), N\(^4\)-methylcytidine (m\(^4\)C), and 5-methylcytidine (m\(^5\)C), respectively. Using in vitro selection, we found several DNA catalysts, which are selectively activated by only one of the three cytidine isomers, and display 10- to 30-fold accelerated cleavage of their targetDeoxyribozymes are emerging as modification-specific endonucleases for the analysis of epigenetic RNA modifications. Here, we report RNA-cleaving deoxyribozymes that differentially respond to the presence of natural methylated cytidines, 3-methylcytidine (m\(^3\)C), N\(^4\)-methylcytidine (m\(^4\)C), and 5-methylcytidine (m\(^5\)C), respectively. Using in vitro selection, we found several DNA catalysts, which are selectively activated by only one of the three cytidine isomers, and display 10- to 30-fold accelerated cleavage of their target m\(^3\)C-, m\(^4\)C- or m\(^5\)C-modified RNA. An additional deoxyribozyme is strongly inhibited by any of the three methylcytidines, but effectively cleaves unmodified RNA. The m\(^X\)C-detecting deoxyribozymes are programmable for the interrogation of natural RNAs of interest, as demonstrated for human mitochondrial tRNAs containing known m\(^3\)C and m\(^5\)C sites. The results underline the potential of synthetic functional DNA to shape highly selective active sites.…
Autor(en): | Anam Liaqat, Maksim V. Sednev, Carina Stiller, Claudia HöbartnerORCiD |
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URN: | urn:nbn:de:bvb:20-opus-254544 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Fakultät für Chemie und Pharmazie / Institut für Organische Chemie |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | Angewandte Chemie International Edition |
Erscheinungsjahr: | 2021 |
Band / Jahrgang: | 60 |
Heft / Ausgabe: | 35 |
Seitenangabe: | 19058-19062 |
Originalveröffentlichung / Quelle: | Angewandte Chemie International Edition 2021, 60, 35, 19058-19062. https://doi.org/10.1002/anie.202106517 |
DOI: | https://doi.org/10.1002/anie.202106517 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 5 Naturwissenschaften und Mathematik / 54 Chemie / 547 Organische Chemie |
Freie Schlagwort(e): | Deoxyribozymes; Epitranscriptomics; RNA Modification; Site-Specific RNA Cleavage; in vitro Selection |
Datum der Freischaltung: | 02.02.2022 |
EU-Projektnummer / Contract (GA) number: | 682586 |
OpenAIRE: | OpenAIRE |
Lizenz (Deutsch): | CC BY-NC-ND: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell, Keine Bearbeitungen 4.0 International |