N\(^6\)-methyladenosine-sensitive RNA-cleaving deoxyribozymes
Please always quote using this URN: urn:nbn:de:bvb:20-opus-171753
- Deoxyribozymes are synthetic enzymes made of DNA that can catalyze the cleavage or formation of phosphodiester bonds and are useful tools for RNA biochemistry. Here we report new RNA-cleaving deoxyribozymes to interrogate the methylation status of target RNAs, thereby providing an alternative method for the biochemical validation of RNA methylation sites containing N\(^6\)-methyladenosine, which is the most wide-spread and extensively investigated natural RNA modification. Using in vitro selection from random DNA, we developed deoxyribozymesDeoxyribozymes are synthetic enzymes made of DNA that can catalyze the cleavage or formation of phosphodiester bonds and are useful tools for RNA biochemistry. Here we report new RNA-cleaving deoxyribozymes to interrogate the methylation status of target RNAs, thereby providing an alternative method for the biochemical validation of RNA methylation sites containing N\(^6\)-methyladenosine, which is the most wide-spread and extensively investigated natural RNA modification. Using in vitro selection from random DNA, we developed deoxyribozymes that are sensitive to the presence of N\(^6\)-methyladenosine in RNA near the cleavage site. One class of these DNA enzymes shows faster cleavage of methylated RNA, while others are strongly inhibited by the modified nucleotide. The general applicability of the new deoxyribozymes is demonstrated for several examples of natural RNA sequences, including a lncRNA and a set of C/D box snoRNAs, which have been suggested to contain m\(^6\)A as a regulatory element that influences RNA folding and protein binding.…
Author: | Maksim V. Sednev, Volodymyr Mykhailiuk, Priyanka Choudhury, Julia Halang, Katherine E. Sloan, Markus T. BohnsackORCiD, Claudia HöbartnerORCiD |
---|---|
URN: | urn:nbn:de:bvb:20-opus-171753 |
Document Type: | Preprint |
Faculties: | Fakultät für Chemie und Pharmazie / Institut für Organische Chemie |
Language: | English |
Parent Title (English): | Angewandte Chemie, International Edition |
Year of Completion: | 2018 |
Source: | Angewandte Chemie International Edition 2018, 57, 15117-15121. DOI: 10.1002/anie.201808745 |
DOI: | https://doi.org/https://doi.org/10.1002/anie.201808745 |
Sonstige beteiligte Institutionen: | International Max Planck Research School Molecular Biology, University of Göttingen, Germany |
Sonstige beteiligte Institutionen: | Department of Molecular Biology, University Medical Center Göttingen, Germany |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften |
Tag: | DNA catalyst; N6-methyladenosine; RNA modification; deoxyribozymes; in vitro selection |
Release Date: | 2018/11/14 |
EU-Project number / Contract (GA) number: | 682586 |
OpenAIRE: | OpenAIRE |
Note: | This is the pre-peer reviewed version of the following article: M.V. Sednev, V. Mykhailiuk, P. Choudhury, J. Halang, K. E. Sloan, M. T. Bohnsack, C. Höbartner, Angew. Chem. Int. Ed. 2018, 57, 15117-15121, which has been published in final form at https://doi.org/10.1002/anie.201808745. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. |
Licence (German): | Deutsches Urheberrecht |