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Circular L-RNA aptamer promotes target recognition and controls gene activity

Rational design of aptamers to incorporate unnatural nucleotides and special chemical moieties can expand their functional complexity and diversity. Spiegelmer (L-RNA aptamer) is a unique class of aptamer that is composed of unnatural L-RNA nucleotides, and so far there are limited L-RNA aptamer can...

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Autores principales: Ji, Danyang, Lyu, Kaixin, Zhao, Haizhou, Kwok, Chun Kit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287958/
https://www.ncbi.nlm.nih.gov/pubmed/34233000
http://dx.doi.org/10.1093/nar/gkab593
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author Ji, Danyang
Lyu, Kaixin
Zhao, Haizhou
Kwok, Chun Kit
author_facet Ji, Danyang
Lyu, Kaixin
Zhao, Haizhou
Kwok, Chun Kit
author_sort Ji, Danyang
collection PubMed
description Rational design of aptamers to incorporate unnatural nucleotides and special chemical moieties can expand their functional complexity and diversity. Spiegelmer (L-RNA aptamer) is a unique class of aptamer that is composed of unnatural L-RNA nucleotides, and so far there are limited L-RNA aptamer candidates and applications being reported. Moreover, the target binding properties of current L-RNA aptamers require significant improvement. Here, using L-Apt.4-1c as an example, we develop a simple and robust strategy to generate the first circular L-RNA aptamer, cycL-Apt.4-1c, quantitatively, demonstrate substantial enhancement in binding affinity and selectivity toward its target, and notably report novel applications of circular L-RNA aptamer in controlling RNA–protein interaction, and gene activity including telomerase activity and gene expression. Our approach and findings will be applicable to any L-RNA aptamers and open up a new avenue for diverse applications.
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spelling pubmed-82879582021-07-19 Circular L-RNA aptamer promotes target recognition and controls gene activity Ji, Danyang Lyu, Kaixin Zhao, Haizhou Kwok, Chun Kit Nucleic Acids Res Chemical Biology and Nucleic Acid Chemistry Rational design of aptamers to incorporate unnatural nucleotides and special chemical moieties can expand their functional complexity and diversity. Spiegelmer (L-RNA aptamer) is a unique class of aptamer that is composed of unnatural L-RNA nucleotides, and so far there are limited L-RNA aptamer candidates and applications being reported. Moreover, the target binding properties of current L-RNA aptamers require significant improvement. Here, using L-Apt.4-1c as an example, we develop a simple and robust strategy to generate the first circular L-RNA aptamer, cycL-Apt.4-1c, quantitatively, demonstrate substantial enhancement in binding affinity and selectivity toward its target, and notably report novel applications of circular L-RNA aptamer in controlling RNA–protein interaction, and gene activity including telomerase activity and gene expression. Our approach and findings will be applicable to any L-RNA aptamers and open up a new avenue for diverse applications. Oxford University Press 2021-07-07 /pmc/articles/PMC8287958/ /pubmed/34233000 http://dx.doi.org/10.1093/nar/gkab593 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Chemical Biology and Nucleic Acid Chemistry
Ji, Danyang
Lyu, Kaixin
Zhao, Haizhou
Kwok, Chun Kit
Circular L-RNA aptamer promotes target recognition and controls gene activity
title Circular L-RNA aptamer promotes target recognition and controls gene activity
title_full Circular L-RNA aptamer promotes target recognition and controls gene activity
title_fullStr Circular L-RNA aptamer promotes target recognition and controls gene activity
title_full_unstemmed Circular L-RNA aptamer promotes target recognition and controls gene activity
title_short Circular L-RNA aptamer promotes target recognition and controls gene activity
title_sort circular l-rna aptamer promotes target recognition and controls gene activity
topic Chemical Biology and Nucleic Acid Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287958/
https://www.ncbi.nlm.nih.gov/pubmed/34233000
http://dx.doi.org/10.1093/nar/gkab593
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