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Structural and dynamic mechanisms for coupled folding and tRNA recognition of a translational T-box riboswitch

T-box riboswitches are unique riboregulators where gene regulation is mediated through interactions between two highly structured RNAs. Despite extensive structural insights, how RNA-RNA interactions drive the folding and structural transitions of T-box to achieve functional conformations remains un...

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Autores principales: Niu, Xiaolin, Xu, Zhonghe, Zhang, Yufan, Zuo, Xiaobing, Chen, Chunlai, Fang, Xianyang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10651847/
https://www.ncbi.nlm.nih.gov/pubmed/37968328
http://dx.doi.org/10.1038/s41467-023-43232-z
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author Niu, Xiaolin
Xu, Zhonghe
Zhang, Yufan
Zuo, Xiaobing
Chen, Chunlai
Fang, Xianyang
author_facet Niu, Xiaolin
Xu, Zhonghe
Zhang, Yufan
Zuo, Xiaobing
Chen, Chunlai
Fang, Xianyang
author_sort Niu, Xiaolin
collection PubMed
description T-box riboswitches are unique riboregulators where gene regulation is mediated through interactions between two highly structured RNAs. Despite extensive structural insights, how RNA-RNA interactions drive the folding and structural transitions of T-box to achieve functional conformations remains unclear. Here, by combining SAXS, single-molecule FRET and computational modeling, we elaborate the folding energy landscape of a translational T-box aptamer consisting of stems I, II and IIA/B, which Mg(2+)-induced global folding and tRNA binding are cooperatively coupled. smFRET measurements reveal that high Mg(2+) stabilizes IIA/B and its stacking on II, which drives the pre-docking of I and II into a competent conformation, subsequent tRNA binding promotes docking of I and II to form a high-affinity tRNA binding groove, of which the essentiality of IIA/B and S-turn in II is substantiated with mutational analysis. We highlight a delicate balance among Mg(2+), the intra- and intermolecular RNA-RNA interactions in modulating RNA folding and function.
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spelling pubmed-106518472023-11-15 Structural and dynamic mechanisms for coupled folding and tRNA recognition of a translational T-box riboswitch Niu, Xiaolin Xu, Zhonghe Zhang, Yufan Zuo, Xiaobing Chen, Chunlai Fang, Xianyang Nat Commun Article T-box riboswitches are unique riboregulators where gene regulation is mediated through interactions between two highly structured RNAs. Despite extensive structural insights, how RNA-RNA interactions drive the folding and structural transitions of T-box to achieve functional conformations remains unclear. Here, by combining SAXS, single-molecule FRET and computational modeling, we elaborate the folding energy landscape of a translational T-box aptamer consisting of stems I, II and IIA/B, which Mg(2+)-induced global folding and tRNA binding are cooperatively coupled. smFRET measurements reveal that high Mg(2+) stabilizes IIA/B and its stacking on II, which drives the pre-docking of I and II into a competent conformation, subsequent tRNA binding promotes docking of I and II to form a high-affinity tRNA binding groove, of which the essentiality of IIA/B and S-turn in II is substantiated with mutational analysis. We highlight a delicate balance among Mg(2+), the intra- and intermolecular RNA-RNA interactions in modulating RNA folding and function. Nature Publishing Group UK 2023-11-15 /pmc/articles/PMC10651847/ /pubmed/37968328 http://dx.doi.org/10.1038/s41467-023-43232-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Niu, Xiaolin
Xu, Zhonghe
Zhang, Yufan
Zuo, Xiaobing
Chen, Chunlai
Fang, Xianyang
Structural and dynamic mechanisms for coupled folding and tRNA recognition of a translational T-box riboswitch
title Structural and dynamic mechanisms for coupled folding and tRNA recognition of a translational T-box riboswitch
title_full Structural and dynamic mechanisms for coupled folding and tRNA recognition of a translational T-box riboswitch
title_fullStr Structural and dynamic mechanisms for coupled folding and tRNA recognition of a translational T-box riboswitch
title_full_unstemmed Structural and dynamic mechanisms for coupled folding and tRNA recognition of a translational T-box riboswitch
title_short Structural and dynamic mechanisms for coupled folding and tRNA recognition of a translational T-box riboswitch
title_sort structural and dynamic mechanisms for coupled folding and trna recognition of a translational t-box riboswitch
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10651847/
https://www.ncbi.nlm.nih.gov/pubmed/37968328
http://dx.doi.org/10.1038/s41467-023-43232-z
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