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Challenges and approaches to predicting RNA with multiple functional structures

The revolution in sequencing technology demands new tools to interpret the genetic code. As in vivo transcriptome-wide chemical probing techniques advance, new challenges emerge in the RNA folding problem. The emphasis on one sequence folding into a single minimum free energy structure is fading as...

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Detalles Bibliográficos
Autor principal: Schroeder, Susan J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6239171/
https://www.ncbi.nlm.nih.gov/pubmed/30143552
http://dx.doi.org/10.1261/rna.067827.118
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author Schroeder, Susan J.
author_facet Schroeder, Susan J.
author_sort Schroeder, Susan J.
collection PubMed
description The revolution in sequencing technology demands new tools to interpret the genetic code. As in vivo transcriptome-wide chemical probing techniques advance, new challenges emerge in the RNA folding problem. The emphasis on one sequence folding into a single minimum free energy structure is fading as a new focus develops on generating RNA structural ensembles and identifying functional structural features in ensembles. This review describes an efficient combinatorially complete method and three free energy minimization approaches to predicting RNA structures with more than one functional fold, as well as two methods for analysis of a thermodynamics-based Boltzmann ensemble of structures. The review then highlights two examples of viral RNA 3′-UTR regions that fold into more than one conformation and have been characterized by single molecule fluorescence energy resonance transfer or NMR spectroscopy. These examples highlight the different approaches and challenges in predicting structure and function from sequence for RNA with multiple biological roles and folds. More well-defined examples and new metrics for measuring differences in RNA structures will guide future improvements in prediction of RNA structure and function from sequence.
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spelling pubmed-62391712019-12-01 Challenges and approaches to predicting RNA with multiple functional structures Schroeder, Susan J. RNA Review The revolution in sequencing technology demands new tools to interpret the genetic code. As in vivo transcriptome-wide chemical probing techniques advance, new challenges emerge in the RNA folding problem. The emphasis on one sequence folding into a single minimum free energy structure is fading as a new focus develops on generating RNA structural ensembles and identifying functional structural features in ensembles. This review describes an efficient combinatorially complete method and three free energy minimization approaches to predicting RNA structures with more than one functional fold, as well as two methods for analysis of a thermodynamics-based Boltzmann ensemble of structures. The review then highlights two examples of viral RNA 3′-UTR regions that fold into more than one conformation and have been characterized by single molecule fluorescence energy resonance transfer or NMR spectroscopy. These examples highlight the different approaches and challenges in predicting structure and function from sequence for RNA with multiple biological roles and folds. More well-defined examples and new metrics for measuring differences in RNA structures will guide future improvements in prediction of RNA structure and function from sequence. Cold Spring Harbor Laboratory Press 2018-12 /pmc/articles/PMC6239171/ /pubmed/30143552 http://dx.doi.org/10.1261/rna.067827.118 Text en © 2018 Schroeder; Published by Cold Spring Harbor Laboratory Press for the RNA Society http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by the RNA Society for the first 12 months after the full-issue publication date (see http://rnajournal.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Review
Schroeder, Susan J.
Challenges and approaches to predicting RNA with multiple functional structures
title Challenges and approaches to predicting RNA with multiple functional structures
title_full Challenges and approaches to predicting RNA with multiple functional structures
title_fullStr Challenges and approaches to predicting RNA with multiple functional structures
title_full_unstemmed Challenges and approaches to predicting RNA with multiple functional structures
title_short Challenges and approaches to predicting RNA with multiple functional structures
title_sort challenges and approaches to predicting rna with multiple functional structures
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6239171/
https://www.ncbi.nlm.nih.gov/pubmed/30143552
http://dx.doi.org/10.1261/rna.067827.118
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