A highly expressed miR-101 isomiR is a functional silencing small RNA

Background: MicroRNAs (miRNAs) are short non-coding regulatory RNAs that control gene expression usually producing translational repression and gene silencing. High-throughput sequencing technologies have revealed heterogeneity at length and sequence level for the majority of mature miRNAs (IsomiRs)...

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Detalles Bibliográficos
Autores: Llorens, Franc, Bañez Coronel, Mónica, Pantano Rubiño, Lorena, 1982-, del Río, José Antonio, Ferrer, Isidre, Estivill, Xavier, 1955-, Martí, Eulàlia
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2013
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:10230/23180
Acceso en línea:http://hdl.handle.net/10230/23180
http://dx.doi.org/10.1186/1471-2164-14-104
Access Level:acceso abierto
Palabra clave:Proteïnes
MicroRNA
miR-101
IsomiR
Ultra-sequencing
Deep-sequencing
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oai_identifier_str oai:recercat.cat:10230/23180
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv A highly expressed miR-101 isomiR is a functional silencing small RNA
title A highly expressed miR-101 isomiR is a functional silencing small RNA
spellingShingle A highly expressed miR-101 isomiR is a functional silencing small RNA
Llorens, Franc
Proteïnes
MicroRNA
miR-101
IsomiR
Ultra-sequencing
Deep-sequencing
title_short A highly expressed miR-101 isomiR is a functional silencing small RNA
title_full A highly expressed miR-101 isomiR is a functional silencing small RNA
title_fullStr A highly expressed miR-101 isomiR is a functional silencing small RNA
title_full_unstemmed A highly expressed miR-101 isomiR is a functional silencing small RNA
title_sort A highly expressed miR-101 isomiR is a functional silencing small RNA
dc.creator.none.fl_str_mv Llorens, Franc
Bañez Coronel, Mónica
Pantano Rubiño, Lorena, 1982-
del Río, José Antonio
Ferrer, Isidre
Estivill, Xavier, 1955-
Martí, Eulàlia
author Llorens, Franc
author_facet Llorens, Franc
Bañez Coronel, Mónica
Pantano Rubiño, Lorena, 1982-
del Río, José Antonio
Ferrer, Isidre
Estivill, Xavier, 1955-
Martí, Eulàlia
author_role author
author2 Bañez Coronel, Mónica
Pantano Rubiño, Lorena, 1982-
del Río, José Antonio
Ferrer, Isidre
Estivill, Xavier, 1955-
Martí, Eulàlia
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Proteïnes
MicroRNA
miR-101
IsomiR
Ultra-sequencing
Deep-sequencing
topic Proteïnes
MicroRNA
miR-101
IsomiR
Ultra-sequencing
Deep-sequencing
description Background: MicroRNAs (miRNAs) are short non-coding regulatory RNAs that control gene expression usually producing translational repression and gene silencing. High-throughput sequencing technologies have revealed heterogeneity at length and sequence level for the majority of mature miRNAs (IsomiRs). Most isomiRs can be explained by variability in either Dicer1 or Drosha cleavage during miRNA biogenesis at 5’ or 3’ of the miRNA (trimming variants). Although isomiRs have been described in different tissues and organisms, their functional validation as modulators of gene expression remains elusive. Here we have characterized the expression and function of a highly abundant miR-101 5’-trimming variant (5’-isomiR-101). Results: The analysis of small RNA sequencing data in several human tissues and cell lines indicates that 5’-isomiR-101 is ubiquitously detected and a highly abundant, especially in the brain. 5’-isomiR-101 was found in Ago-2 immunocomplexes and complementary approaches showed that 5’-isomiR-101 interacted with different members of the silencing (RISC) complex. In addition, 5’-isomiR-101 decreased the expression of five validated miR-101 targets, suggesting that it is a functional variant. Both the binding to RISC members and the degree of silencing were less efficient for 5’-isomiR-101 compared with miR-101. For some targets, both miR-101 and 5’-isomiR-101 significantly decreased protein expression with no changes in the respective mRNA levels. Although a high number of overlapping predicted targets suggest similar targeted biological pathways, a correlation analysis of the expression profiles of miR-101 variants and predicted mRNA targets in human brains at different ages, suggest specific functions for miR-101- and 5’-isomiR-101. Conclusions: These results suggest that isomiRs are functional variants and further indicate that for a given miRNA, the different isomiRs may contribute to the overall effect as quantitative and qualitative fine-tuners of gene expression.
publishDate 2013
dc.date.none.fl_str_mv 2013
2015
2015
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/10230/23180
http://dx.doi.org/10.1186/1471-2164-14-104
url http://hdl.handle.net/10230/23180
http://dx.doi.org/10.1186/1471-2164-14-104
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv BMC Genomics. 2013; 14: 104
info:eu-repo/grantAgreement/ES/PI02008-81367/
info:eu-repo/grantAgreement/ES/3PN/PI2011-02036
info:eu-repo/grantAgreement/ES/3PN/PI2011-00968
info:eu-repo/grantAgreement/ES/3PN/SAF2008-00357
info:eu-repo/grantAgreement/ES/3PN/ BFU2009-10848
info:eu-repo/grantAgreement/ES/3PN/BFU2012-32617
info:eu-repo/grantAgreement/EC/FP7/037900
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/2.0
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/2.0
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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spelling A highly expressed miR-101 isomiR is a functional silencing small RNALlorens, FrancBañez Coronel, MónicaPantano Rubiño, Lorena, 1982-del Río, José AntonioFerrer, IsidreEstivill, Xavier, 1955-Martí, EulàliaProteïnesMicroRNAmiR-101IsomiRUltra-sequencingDeep-sequencingBackground: MicroRNAs (miRNAs) are short non-coding regulatory RNAs that control gene expression usually producing translational repression and gene silencing. High-throughput sequencing technologies have revealed heterogeneity at length and sequence level for the majority of mature miRNAs (IsomiRs). Most isomiRs can be explained by variability in either Dicer1 or Drosha cleavage during miRNA biogenesis at 5’ or 3’ of the miRNA (trimming variants). Although isomiRs have been described in different tissues and organisms, their functional validation as modulators of gene expression remains elusive. Here we have characterized the expression and function of a highly abundant miR-101 5’-trimming variant (5’-isomiR-101). Results: The analysis of small RNA sequencing data in several human tissues and cell lines indicates that 5’-isomiR-101 is ubiquitously detected and a highly abundant, especially in the brain. 5’-isomiR-101 was found in Ago-2 immunocomplexes and complementary approaches showed that 5’-isomiR-101 interacted with different members of the silencing (RISC) complex. In addition, 5’-isomiR-101 decreased the expression of five validated miR-101 targets, suggesting that it is a functional variant. Both the binding to RISC members and the degree of silencing were less efficient for 5’-isomiR-101 compared with miR-101. For some targets, both miR-101 and 5’-isomiR-101 significantly decreased protein expression with no changes in the respective mRNA levels. Although a high number of overlapping predicted targets suggest similar targeted biological pathways, a correlation analysis of the expression profiles of miR-101 variants and predicted mRNA targets in human brains at different ages, suggest specific functions for miR-101- and 5’-isomiR-101. Conclusions: These results suggest that isomiRs are functional variants and further indicate that for a given miRNA, the different isomiRs may contribute to the overall effect as quantitative and qualitative fine-tuners of gene expression.This work was supported by the Spanish Government and FEDER (Fondo Europeo de Desarrollo Regional): PN de I+D+I 2008–2011, PI081367 (E. Martí) and PN de I+D+I 2012–2015 PI11/02036 (E. Martí), PI1100968 (I. Ferrer) Instituto Carlos III –ISCIII-, Subdirección General de Evaluación y Fomento de la Investigación, SAF2008-00357 (X. Estivill) Ministerio de Economia y competitividad, BESAD (JA de Río), DEMTEST Joint Programing of Neurodegenerative diseases (EU) (JA del Río), MICINN BFU2009-10848 and BFU2012-32617 (JA del Río), FP7-PRIORITY (JA del Río), Eusko Fundazioa (BIO12/AL/004) (JA del Río) and Generalitat de Catalunya SGR2009-366 (JA del Río); the Sixth Framework Programme of the European Commission through the SIROCCO integrated project LSHG-CT-2006-037900. The Spanish Government supports: M. Bañez-Coronel (Sara Borrell Postdoctoral contract, ISCIII) and partially supports E.Martí (Programa Miguel Servet, ISCIII)BioMed Central201520152013info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/23180http://dx.doi.org/10.1186/1471-2164-14-104reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésBMC Genomics. 2013; 14: 104info:eu-repo/grantAgreement/ES/PI02008-81367/info:eu-repo/grantAgreement/ES/3PN/PI2011-02036info:eu-repo/grantAgreement/ES/3PN/PI2011-00968info:eu-repo/grantAgreement/ES/3PN/SAF2008-00357info:eu-repo/grantAgreement/ES/3PN/ BFU2009-10848info:eu-repo/grantAgreement/ES/3PN/BFU2012-32617info:eu-repo/grantAgreement/EC/FP7/037900© 2013 Llorens et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.http://creativecommons.org/licenses/by/2.0info:eu-repo/semantics/openAccessoai:recercat.cat:10230/231802026-05-29T05:05:01Z
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