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RNA‐Cleaving Deoxyribozymes Differentiate Methylated Cytidine Isomers in RNA

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‐...

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Autores principales: Liaqat, Anam, Sednev, Maksim V., Stiller, Carina, Höbartner, Claudia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8457104/
https://www.ncbi.nlm.nih.gov/pubmed/34185947
http://dx.doi.org/10.1002/anie.202106517
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author Liaqat, Anam
Sednev, Maksim V.
Stiller, Carina
Höbartner, Claudia
author_facet Liaqat, Anam
Sednev, Maksim V.
Stiller, Carina
Höbartner, Claudia
author_sort Liaqat, Anam
collection PubMed
description 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 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.
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spelling pubmed-84571042021-09-27 RNA‐Cleaving Deoxyribozymes Differentiate Methylated Cytidine Isomers in RNA Liaqat, Anam Sednev, Maksim V. Stiller, Carina Höbartner, Claudia Angew Chem Int Ed Engl Communications 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 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. John Wiley and Sons Inc. 2021-07-26 2021-08-23 /pmc/articles/PMC8457104/ /pubmed/34185947 http://dx.doi.org/10.1002/anie.202106517 Text en © 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Communications
Liaqat, Anam
Sednev, Maksim V.
Stiller, Carina
Höbartner, Claudia
RNA‐Cleaving Deoxyribozymes Differentiate Methylated Cytidine Isomers in RNA
title RNA‐Cleaving Deoxyribozymes Differentiate Methylated Cytidine Isomers in RNA
title_full RNA‐Cleaving Deoxyribozymes Differentiate Methylated Cytidine Isomers in RNA
title_fullStr RNA‐Cleaving Deoxyribozymes Differentiate Methylated Cytidine Isomers in RNA
title_full_unstemmed RNA‐Cleaving Deoxyribozymes Differentiate Methylated Cytidine Isomers in RNA
title_short RNA‐Cleaving Deoxyribozymes Differentiate Methylated Cytidine Isomers in RNA
title_sort rna‐cleaving deoxyribozymes differentiate methylated cytidine isomers in rna
topic Communications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8457104/
https://www.ncbi.nlm.nih.gov/pubmed/34185947
http://dx.doi.org/10.1002/anie.202106517
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