TY  - JOUR
A1  - Liaqat, Anam
A1  - Sednev, Maksim V.
A1  - Stiller, Carina
A1  - Höbartner, Claudia
T1  - RNA-cleaving deoxyribozymes differentiate methylated cytidine isomers in RNA
T2  - Angewandte Chemie International Edition
N2  - 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 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.
KW  - organic chemistry
KW  - site-specific RNA cleavage
KW  - deoxyribozymes
KW  - epitranscriptomics
KW  - in vitro selection
KW  - RNA modification
Y1  - 2021
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/25651
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-256519
VL  - 60
ER  -