N\(^6\)-Isopentenyladenosine in RNA Determines the Cleavage Site of Endonuclease Deoxyribozymes
Please always quote using this URN: urn:nbn:de:bvb:20-opus-212121
- RNA-cleaving deoxyribozymes can serve as selective sensors and catalysts to examine the modification state of RNA. However, site-specific endonuclease deoxyribozymes that selectively cleave posttranscriptionally modified RNA are extremely rare and their specificity over unmodified RNA is low. In this study, we report that the native tRNA modification N\(^6\)-isopentenyladenosine (i\(^6\)A) strongly enhances the specificity and has the power to reconfigure the active site of an RNA-cleaving deoxyribozyme. Using in vitro selection, we identifiedRNA-cleaving deoxyribozymes can serve as selective sensors and catalysts to examine the modification state of RNA. However, site-specific endonuclease deoxyribozymes that selectively cleave posttranscriptionally modified RNA are extremely rare and their specificity over unmodified RNA is low. In this study, we report that the native tRNA modification N\(^6\)-isopentenyladenosine (i\(^6\)A) strongly enhances the specificity and has the power to reconfigure the active site of an RNA-cleaving deoxyribozyme. Using in vitro selection, we identified a DNA enzyme that cleaves i\(^6\)A-modified RNA at least 2500-fold faster than unmodified RNA. Another deoxyribozyme shows unique and unprecedented behaviour by shifting its cleavage site in the presence of the i\(^6\)A RNA modification. Together with deoxyribozymes that are strongly inhibited by i\(^6\)A, these results highlight intricate ways of modulating the catalytic activity of DNA by posttranscriptional RNA modifications.…
Author: | Anam Liaqat, Carina Stiller, Manuela Michel, Maksim V. Sednev, Claudia HöbartnerORCiD |
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URN: | urn:nbn:de:bvb:20-opus-212121 |
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: | 2020 |
Edition: | Early View |
Source: | Angewandte Chemie International Edition 2020. doi:10.1002/anie.202006218 |
DOI: | https://doi.org/10.1002/ange.202006218 |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 54 Chemie / 547 Organische Chemie |
Tag: | Deoxyribozymes; Epitranscriptomics; RNA modification; in vitro selection; site-specific RNA cleavage |
Release Date: | 2020/09/28 |
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 |