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Progress toward SHAPE Constrained Computational Prediction of Tertiary Interactions in RNA Structure

As more sequencing data accumulate and novel puzzling genetic regulations are discovered, the need for accurate automated modeling of RNA structure increases. RNA structure modeling from chemical probing experiments has made tremendous progress, however accurately predicting large RNA structures is...

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Autores principales: De Bisschop, Grégoire, Allouche, Delphine, Frezza, Elisa, Masquida, Benoît, Ponty, Yann, Will, Sebastian, Sargueil, Bruno
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8628965/
https://www.ncbi.nlm.nih.gov/pubmed/34842779
http://dx.doi.org/10.3390/ncrna7040071
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author De Bisschop, Grégoire
Allouche, Delphine
Frezza, Elisa
Masquida, Benoît
Ponty, Yann
Will, Sebastian
Sargueil, Bruno
author_facet De Bisschop, Grégoire
Allouche, Delphine
Frezza, Elisa
Masquida, Benoît
Ponty, Yann
Will, Sebastian
Sargueil, Bruno
author_sort De Bisschop, Grégoire
collection PubMed
description As more sequencing data accumulate and novel puzzling genetic regulations are discovered, the need for accurate automated modeling of RNA structure increases. RNA structure modeling from chemical probing experiments has made tremendous progress, however accurately predicting large RNA structures is still challenging for several reasons: RNA are inherently flexible and often adopt many energetically similar structures, which are not reliably distinguished by the available, incomplete thermodynamic model. Moreover, computationally, the problem is aggravated by the relevance of pseudoknots and non-canonical base pairs, which are hardly predicted efficiently. To identify nucleotides involved in pseudoknots and non-canonical interactions, we scrutinized the SHAPE reactivity of each nucleotide of the 188 nt long lariat-capping ribozyme under multiple conditions. Reactivities analyzed in the light of the X-ray structure were shown to report accurately the nucleotide status. Those that seemed paradoxical were rationalized by the nucleotide behavior along molecular dynamic simulations. We show that valuable information on intricate interactions can be deduced from probing with different reagents, and in the presence or absence of Mg(2+). Furthermore, probing at increasing temperature was remarkably efficient at pointing to non-canonical interactions and pseudoknot pairings. The possibilities of following such strategies to inform structure modeling software are discussed.
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spelling pubmed-86289652021-11-30 Progress toward SHAPE Constrained Computational Prediction of Tertiary Interactions in RNA Structure De Bisschop, Grégoire Allouche, Delphine Frezza, Elisa Masquida, Benoît Ponty, Yann Will, Sebastian Sargueil, Bruno Noncoding RNA Article As more sequencing data accumulate and novel puzzling genetic regulations are discovered, the need for accurate automated modeling of RNA structure increases. RNA structure modeling from chemical probing experiments has made tremendous progress, however accurately predicting large RNA structures is still challenging for several reasons: RNA are inherently flexible and often adopt many energetically similar structures, which are not reliably distinguished by the available, incomplete thermodynamic model. Moreover, computationally, the problem is aggravated by the relevance of pseudoknots and non-canonical base pairs, which are hardly predicted efficiently. To identify nucleotides involved in pseudoknots and non-canonical interactions, we scrutinized the SHAPE reactivity of each nucleotide of the 188 nt long lariat-capping ribozyme under multiple conditions. Reactivities analyzed in the light of the X-ray structure were shown to report accurately the nucleotide status. Those that seemed paradoxical were rationalized by the nucleotide behavior along molecular dynamic simulations. We show that valuable information on intricate interactions can be deduced from probing with different reagents, and in the presence or absence of Mg(2+). Furthermore, probing at increasing temperature was remarkably efficient at pointing to non-canonical interactions and pseudoknot pairings. The possibilities of following such strategies to inform structure modeling software are discussed. MDPI 2021-11-05 /pmc/articles/PMC8628965/ /pubmed/34842779 http://dx.doi.org/10.3390/ncrna7040071 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
De Bisschop, Grégoire
Allouche, Delphine
Frezza, Elisa
Masquida, Benoît
Ponty, Yann
Will, Sebastian
Sargueil, Bruno
Progress toward SHAPE Constrained Computational Prediction of Tertiary Interactions in RNA Structure
title Progress toward SHAPE Constrained Computational Prediction of Tertiary Interactions in RNA Structure
title_full Progress toward SHAPE Constrained Computational Prediction of Tertiary Interactions in RNA Structure
title_fullStr Progress toward SHAPE Constrained Computational Prediction of Tertiary Interactions in RNA Structure
title_full_unstemmed Progress toward SHAPE Constrained Computational Prediction of Tertiary Interactions in RNA Structure
title_short Progress toward SHAPE Constrained Computational Prediction of Tertiary Interactions in RNA Structure
title_sort progress toward shape constrained computational prediction of tertiary interactions in rna structure
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8628965/
https://www.ncbi.nlm.nih.gov/pubmed/34842779
http://dx.doi.org/10.3390/ncrna7040071
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