RNA-cleaving deoxyribozymes differentiate methylated cytidine isomers in RNA
Please always quote using this URN: urn:nbn:de:bvb:20-opus-256519
- 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 mXC-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.…
Author: | Anam Liaqat, Dr. Maksim V. SednevORCiD, Carina Stiller, Prof. Dr. Claudia HöbartnerORCiD |
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URN: | urn:nbn:de:bvb:20-opus-256519 |
Document Type: | Journal article |
Faculties: | Fakultät für Chemie und Pharmazie / Institut für Organische Chemie |
Language: | English |
Parent Title (English): | Angewandte Chemie International Edition |
Year of Completion: | 2021 |
Volume: | 60 |
Article Number: | 35 |
Pagenumber: | 19058–19062 |
Source: | Angewandte Chemie International Edition (2021) 60:35, 19058–19062. DOI: 10.1002/anie.202106517 |
DOI: | https://doi.org/10.1002/anie.202106517 |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 54 Chemie / 547 Organische Chemie |
Tag: | RNA modification; deoxyribozymes; epitranscriptomics; in vitro selection; organic chemistry; site-specific RNA cleavage |
Release Date: | 2022/02/24 |
EU-Project number / Contract (GA) number: | 682586 |
OpenAIRE: | OpenAIRE |
Licence (German): | CC BY-NC-ND: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell, Keine Bearbeitungen 4.0 International |