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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| Format: | Article |
| Language: | English |
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MDPI AG
2021-11-01
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| Series: | Non-Coding RNA |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2311-553X/7/4/71 |
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| author | Grégoire De Bisschop Delphine Allouche Elisa Frezza Benoît Masquida Yann Ponty Sebastian Will Bruno Sargueil |
| author_facet | Grégoire De Bisschop Delphine Allouche Elisa Frezza Benoît Masquida Yann Ponty Sebastian Will Bruno Sargueil |
| author_sort | Grégoire De Bisschop |
| collection | DOAJ |
| 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<sup>2+</sup>. 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. |
| first_indexed | 2024-03-10T03:25:19Z |
| format | Article |
| id | doaj.art-610830887fb04506bac3231db6f2d480 |
| institution | Directory Open Access Journal |
| issn | 2311-553X |
| language | English |
| last_indexed | 2024-03-10T03:25:19Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Non-Coding RNA |
| spelling | doaj.art-610830887fb04506bac3231db6f2d4802023-11-23T09:53:07ZengMDPI AGNon-Coding RNA2311-553X2021-11-01747110.3390/ncrna7040071Progress toward SHAPE Constrained Computational Prediction of Tertiary Interactions in RNA StructureGrégoire De Bisschop0Delphine Allouche1Elisa Frezza2Benoît Masquida3Yann Ponty4Sebastian Will5Bruno Sargueil6Université de Paris, CNRS, UMR 8038/CiTCoM, F-75006 Paris, FranceUniversité de Paris, CNRS, UMR 8038/CiTCoM, F-75006 Paris, FranceUniversité de Paris, CNRS, UMR 8038/CiTCoM, F-75006 Paris, FranceUniversité de Strasbourg, CNRS UMR7156 GMGM, 67084 Strasbourg, FranceEcole Polytechnique, CNRS UMR 7161, LIX, 91120 Palaiseau, FranceEcole Polytechnique, CNRS UMR 7161, LIX, 91120 Palaiseau, FranceUniversité de Paris, CNRS, UMR 8038/CiTCoM, F-75006 Paris, FranceAs 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<sup>2+</sup>. 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.https://www.mdpi.com/2311-553X/7/4/71ribozymeshape probingRNA structure modeling |
| spellingShingle | Grégoire De Bisschop Delphine Allouche Elisa Frezza Benoît Masquida Yann Ponty Sebastian Will Bruno Sargueil Progress toward SHAPE Constrained Computational Prediction of Tertiary Interactions in RNA Structure Non-Coding RNA ribozyme shape probing RNA structure modeling |
| 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 | ribozyme shape probing RNA structure modeling |
| url | https://www.mdpi.com/2311-553X/7/4/71 |
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