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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-8628965 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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