Secondary structure impacts patterns of selection in human IncRNAs

Background: Metazoans transcribe many long non-coding RNAs (lncRNAs) that are poorly conserved and whose function remains unknown. This has raised the questions of what fraction of the predicted lncRNAs is actually functional, and whether selection can effectively constrain lncRNAs in species with s...

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Detalles Bibliográficos
Autores: Pegueroles Queralt, Maria Cinta, Gabaldón Estevan, Juan Antonio, 1973-
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2016
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/27572
Acceso en línea:http://hdl.handle.net/10230/27572
http://dx.doi.org/10.1186/s12915-016-0283-0
Access Level:acceso abierto
Palabra clave:lncRNA
Purifying selection
Divergence
Polymorphism
Secondary structure
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spelling Secondary structure impacts patterns of selection in human IncRNAsPegueroles Queralt, Maria CintaGabaldón Estevan, Juan Antonio, 1973-lncRNAPurifying selectionDivergencePolymorphismSecondary structureBackground: Metazoans transcribe many long non-coding RNAs (lncRNAs) that are poorly conserved and whose function remains unknown. This has raised the questions of what fraction of the predicted lncRNAs is actually functional, and whether selection can effectively constrain lncRNAs in species with small effective population sizes such as human populations. Results: Here we evaluate signatures of selection in human lncRNAs using inter-specific data and intra-specific comparisons from five major populations, as well as by assessing relationships between sequence variation and predictions of secondary structure. In all analyses we included a reference of functionally characterized lncRNAs. Altogether, our results show compelling evidence of recent purifying selection acting on both characterized and predicted lncRNAs. We found that RNA secondary structure constrains sequence variation in lncRNAs, so that polymorphisms are depleted in paired regions with low accessibility and tend to be neutral with respect to structural stability. Conclusions: Important implications of our results are that secondary structure plays a role in the functionality of lncRNAs, and that the set of predicted lncRNAs contains a large fraction of functional ones that may play key roles that remain to be discovered.Toni Gabaldon's (TG’s) group acknowledges support from the Spanish Ministry of Economy and Competitiveness grants “Centro de Excelencia Severo Ochoa 2013-2017” SEV-2012-0208 and BFU2015-67107, cofounded by the European Regional Development Fund (ERDF); from the European Union and ERC Seventh Framework Programme (FP7/2007-2013) under grant agreements FP7-PEOPLE-2013-ITN-606786 and ERC-2012-StG-310325; and a grant from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement number H2020-MSCA-ITN-2014-642095.BioMed Central201620162016info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/27572http://dx.doi.org/10.1186/s12915-016-0283-0reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésBMC Biology. 2016;14:60info:eu-repo/grantAgreement/ES/1PE/BFU2015-67107info:eu-repo/grantAgreement/EC/FP7/606786info:eu-repo/grantAgreement/EC/H2020/642095info:eu-repo/grantAgreement/EC/FP7/310325© 2016 Pegueroles and Gabaldon. Open Access. This 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.http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/275722026-05-29T05:05:01Z
dc.title.none.fl_str_mv Secondary structure impacts patterns of selection in human IncRNAs
title Secondary structure impacts patterns of selection in human IncRNAs
spellingShingle Secondary structure impacts patterns of selection in human IncRNAs
Pegueroles Queralt, Maria Cinta
lncRNA
Purifying selection
Divergence
Polymorphism
Secondary structure
title_short Secondary structure impacts patterns of selection in human IncRNAs
title_full Secondary structure impacts patterns of selection in human IncRNAs
title_fullStr Secondary structure impacts patterns of selection in human IncRNAs
title_full_unstemmed Secondary structure impacts patterns of selection in human IncRNAs
title_sort Secondary structure impacts patterns of selection in human IncRNAs
dc.creator.none.fl_str_mv Pegueroles Queralt, Maria Cinta
Gabaldón Estevan, Juan Antonio, 1973-
author Pegueroles Queralt, Maria Cinta
author_facet Pegueroles Queralt, Maria Cinta
Gabaldón Estevan, Juan Antonio, 1973-
author_role author
author2 Gabaldón Estevan, Juan Antonio, 1973-
author2_role author
dc.subject.none.fl_str_mv lncRNA
Purifying selection
Divergence
Polymorphism
Secondary structure
topic lncRNA
Purifying selection
Divergence
Polymorphism
Secondary structure
description Background: Metazoans transcribe many long non-coding RNAs (lncRNAs) that are poorly conserved and whose function remains unknown. This has raised the questions of what fraction of the predicted lncRNAs is actually functional, and whether selection can effectively constrain lncRNAs in species with small effective population sizes such as human populations. Results: Here we evaluate signatures of selection in human lncRNAs using inter-specific data and intra-specific comparisons from five major populations, as well as by assessing relationships between sequence variation and predictions of secondary structure. In all analyses we included a reference of functionally characterized lncRNAs. Altogether, our results show compelling evidence of recent purifying selection acting on both characterized and predicted lncRNAs. We found that RNA secondary structure constrains sequence variation in lncRNAs, so that polymorphisms are depleted in paired regions with low accessibility and tend to be neutral with respect to structural stability. Conclusions: Important implications of our results are that secondary structure plays a role in the functionality of lncRNAs, and that the set of predicted lncRNAs contains a large fraction of functional ones that may play key roles that remain to be discovered.
publishDate 2016
dc.date.none.fl_str_mv 2016
2016
2016
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/27572
http://dx.doi.org/10.1186/s12915-016-0283-0
url http://hdl.handle.net/10230/27572
http://dx.doi.org/10.1186/s12915-016-0283-0
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv BMC Biology. 2016;14:60
info:eu-repo/grantAgreement/ES/1PE/BFU2015-67107
info:eu-repo/grantAgreement/EC/FP7/606786
info:eu-repo/grantAgreement/EC/H2020/642095
info:eu-repo/grantAgreement/EC/FP7/310325
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
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