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

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• dc.contributor.author Llorens, Francca
• dc.contributor.author Bañez Coronel, Mónicaca
• dc.contributor.author Pantano Rubiño, Lorena, 1982-ca
• dc.contributor.author del Río, José Antonioca
• dc.contributor.author Ferrer, Isidreca
• dc.contributor.author Estivill, Xavier, 1955-ca
• dc.contributor.author Martí, Eulàliaca
• dc.date.accessioned 2015-03-16T08:15:39Z
• dc.date.available 2015-03-16T08:15:39Z
• dc.date.issued 2013ca
• dc.description.abstract 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.en
• dc.description.sponsorship 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)en
• dc.format.mimetype application/pdfca
• dc.identifier.citation Llorens F, Bañez-Coronel M, Pantano L, del Río JA, Ferrer I, Estivill X, Martí E. A highly expressed miR-101 isomiR is a functional silencing small RNA. BMC Genomics. 2013; 14: 104. DOI 10.1186/1471-2164-14-104ca
• dc.identifier.doi http://dx.doi.org/10.1186/1471-2164-14-104
• dc.identifier.issn 1471-2164ca
• dc.identifier.uri http://hdl.handle.net/10230/23180
• dc.language.iso engca
• dc.publisher BioMed Centralca
• dc.relation.ispartof BMC Genomics. 2013; 14: 104
• dc.relation.projectID info:eu-repo/grantAgreement/ES/PI02008-81367
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/PI2011-02036
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/PI2011-00968
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2008-00357
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/ BFU2009-10848
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2012-32617
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/037900
• dc.rights © 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.ca
• dc.rights.accessRights info:eu-repo/semantics/openAccessca
• dc.rights.uri http://creativecommons.org/licenses/by/2.0
• dc.subject.keyword MicroRNAen
• dc.subject.keyword miR-101en
• dc.subject.keyword IsomiRen
• dc.subject.keyword Ultra-sequencingen
• dc.subject.keyword Deep-sequencingen
• dc.subject.other Proteïnesca
• dc.title A highly expressed miR-101 isomiR is a functional silencing small RNAca
• dc.type info:eu-repo/semantics/articleca
• dc.type.version info:eu-repo/semantics/publishedVersionca