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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‐...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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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. |
format | Online Article Text |
id | pubmed-8457104 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
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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