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Finding RNA structure in the unstructured RBPome
BACKGROUND: RNA-binding proteins (RBPs) play vital roles in many processes in the cell. Different RBPs bind RNA with different sequence and structure specificities. While sequence specificities for a large set of 205 RBPs have been reported through the RNAcompete compendium, structure specificities...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5819699/ https://www.ncbi.nlm.nih.gov/pubmed/29463232 http://dx.doi.org/10.1186/s12864-018-4540-1 |
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author | Orenstein, Yaron Ohler, Uwe Berger, Bonnie |
author_facet | Orenstein, Yaron Ohler, Uwe Berger, Bonnie |
author_sort | Orenstein, Yaron |
collection | PubMed |
description | BACKGROUND: RNA-binding proteins (RBPs) play vital roles in many processes in the cell. Different RBPs bind RNA with different sequence and structure specificities. While sequence specificities for a large set of 205 RBPs have been reported through the RNAcompete compendium, structure specificities are known for only a small fraction. The main limitation lies in the design of the RNAcompete technology, which tests RBP binding against unstructured RNA probes, making it difficult to infer structural preferences from these data. We recently developed RCK, an algorithm to infer sequence and structural binding models from RNAcompete data. The set of binding models enables, for the first time, a large-scale assessment of RNA structure in the RBPome. RESULTS: We re-validate and uncover the role of RNA structure in the RPBome through novel analysis of the largest-scale dataset to date. First, we show that RNA structure exists in presumably unstructured RNA probes and that its variability is correlated with RNA-binding. Second, we examine the structural binding preferences of RBPs and discover an overall preference to bind RNA loops. Third, we significantly improve protein-binding prediction using RNA structure, both in vitro and in vivo. Lastly, we demonstrate that RNA structural binding preferences can be inferred for new proteins from solely their amino acid content. CONCLUSIONS: By counter-intuitively demonstrating through our analysis that we can predict both the RNA structure of and RBP binding to these putatively unstructured RNAs, we transform a compendium of RNA-binding proteins into a valuable resource for structure-based binding models. We uncover the important role RNA structure plays in protein-RNA interaction for hundreds of RNA-binding proteins. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12864-018-4540-1) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5819699 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-58196992018-02-26 Finding RNA structure in the unstructured RBPome Orenstein, Yaron Ohler, Uwe Berger, Bonnie BMC Genomics Research Article BACKGROUND: RNA-binding proteins (RBPs) play vital roles in many processes in the cell. Different RBPs bind RNA with different sequence and structure specificities. While sequence specificities for a large set of 205 RBPs have been reported through the RNAcompete compendium, structure specificities are known for only a small fraction. The main limitation lies in the design of the RNAcompete technology, which tests RBP binding against unstructured RNA probes, making it difficult to infer structural preferences from these data. We recently developed RCK, an algorithm to infer sequence and structural binding models from RNAcompete data. The set of binding models enables, for the first time, a large-scale assessment of RNA structure in the RBPome. RESULTS: We re-validate and uncover the role of RNA structure in the RPBome through novel analysis of the largest-scale dataset to date. First, we show that RNA structure exists in presumably unstructured RNA probes and that its variability is correlated with RNA-binding. Second, we examine the structural binding preferences of RBPs and discover an overall preference to bind RNA loops. Third, we significantly improve protein-binding prediction using RNA structure, both in vitro and in vivo. Lastly, we demonstrate that RNA structural binding preferences can be inferred for new proteins from solely their amino acid content. CONCLUSIONS: By counter-intuitively demonstrating through our analysis that we can predict both the RNA structure of and RBP binding to these putatively unstructured RNAs, we transform a compendium of RNA-binding proteins into a valuable resource for structure-based binding models. We uncover the important role RNA structure plays in protein-RNA interaction for hundreds of RNA-binding proteins. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12864-018-4540-1) contains supplementary material, which is available to authorized users. BioMed Central 2018-02-20 /pmc/articles/PMC5819699/ /pubmed/29463232 http://dx.doi.org/10.1186/s12864-018-4540-1 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Orenstein, Yaron Ohler, Uwe Berger, Bonnie Finding RNA structure in the unstructured RBPome |
title | Finding RNA structure in the unstructured RBPome |
title_full | Finding RNA structure in the unstructured RBPome |
title_fullStr | Finding RNA structure in the unstructured RBPome |
title_full_unstemmed | Finding RNA structure in the unstructured RBPome |
title_short | Finding RNA structure in the unstructured RBPome |
title_sort | finding rna structure in the unstructured rbpome |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5819699/ https://www.ncbi.nlm.nih.gov/pubmed/29463232 http://dx.doi.org/10.1186/s12864-018-4540-1 |
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