Evidence for the biogenesis of more than 1,000 novel human microRNAs

Friedländer, Marc R.; Lizano González, Esther, 1974-; Houben, Anna J.; Bezdan, Daniela; Bañez Coronel, Mónica; Kudla, Grzegorz; Mateu Huertas, Elisabet, 1983-; Kagerbauer, Birgit; González Morilla, Justo; Chen, Kevin C; LeProust, Emily M; Martí Puig, Eulàlia; Estivill, Xavier, 1955-

Evidence for the biogenesis of more than 1,000 novel human microRNAs

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dc.contributor.author Friedländer, Marc R.ca
dc.contributor.author Lizano González, Esther, 1974-ca
dc.contributor.author Houben, Anna J.ca
dc.contributor.author Bezdan, Danielaca
dc.contributor.author Bañez Coronel, Mónicaca
dc.contributor.author Kudla, Grzegorzca
dc.contributor.author Mateu Huertas, Elisabet, 1983-ca
dc.contributor.author Kagerbauer, Birgitca
dc.contributor.author González Morilla, Justoca
dc.contributor.author Chen, Kevin Cca
dc.contributor.author LeProust, Emily Mca
dc.contributor.author Martí Puig, Eulàliaca
dc.contributor.author Estivill, Xavier, 1955-ca
dc.date.accessioned 2015-03-19T08:37:48Z
dc.date.available 2015-03-19T08:37:48Z
dc.date.issued 2014ca
dc.description.abstract Background: MicroRNAs (miRNAs) are established regulators of development, cell identity and disease. Although nearly two thousand human miRNA genes are known and new ones are continuously discovered, no attempt has been made to gauge the total miRNA content of the human genome. Results: Employing an innovative computational method on massively pooled small RNA sequencing data, we report 2,469 novel human miRNA candidates of which 1,098 are validated by in-house and published experiments. Almost 300 candidates are robustly expressed in a neuronal cell system and are regulated during differentiation or when biogenesis factors Dicer, Drosha, DGCR8 or Ago2 are silenced. To improve expression profiling, we devised a quantitative miRNA capture system. In a kidney cell system, 400 candidates interact with DGCR8 at transcript positions that suggest miRNA hairpin recognition, and 1,000 of the new miRNA candidates interact with Ago1 or Ago2, indicating that they are directly bound by miRNA effector proteins. From kidney cell CLASH experiments, in which miRNA-target pairs are ligated and sequenced, we observe hundreds of interactions between novel miRNAs and mRNA targets. The novel miRNA candidates are specifically but lowly expressed, raising the possibility that not all may be functional. Interestingly, the majority are evolutionarily young and overrepresented in the human brain. Conclusions: In summary, we present evidence that the complement of human miRNA genes is substantially larger than anticipated, and that more are likely to be discovered in the future as more tissues and experimental conditions are sequenced to greater depth.en
dc.description.sponsorship This project was funded by the Spanish Plan Nacional SAF2008-00357 (NOVADIS); the Generalitat de Catalunya AGAUR 2009 SGR-1502; the Instituto de Salud Carlos III (FIS/FEDER PI11/00733); National Institutes of Health (R00HG004515 to KCC) and the European Commission 7th Framework Program, Projects N. 03790 (SIROCCO), N. 282510 (BLUEPRINT), N. 261123 (GEUVADIS) and N. 262055 (ESGI). MRF is supported by EMBO Long-Term fellowship ALTF 225–2011; EL is supported by the ICGC CLL-Genome project funded by the Spanish Ministry of Economy and Competiveness through the Instituto de Salud Carlos III. AJSH is a Marie Curie postdoctoral fellow supported by the European Commission 7th Framework Program under grant agreement N. 330133. MB-C is a Sara Borrell postdoctoral fellow supported by the Spanish Ministry of Economy and Competiveness. GK was supported by the Wellcome Trust Grant 097383 and by the MRC. EM–H is a PhD student from LaCaixaen
dc.format.mimetype application/pdfca
dc.identifier.citation Friedländer MR, Lizano E, Houben AJ, Bezdan D, Báñez-Coronel M, Kudla G, Mateu-Huertas E, Kagerbauer B, González J, Chen KC, LeProust EM, Martí E, Estivill X. Evidence for the biogenesis of more than 1,000 novel human microRNAs. Genome Biology. 2014; 15: R57. DOI 10.1186/gb-2014-15-4-r57ca
dc.identifier.doi http://dx.doi.org/10.1186/gb-2014-15-4-r57
dc.identifier.issn 1465-6906ca
dc.identifier.uri http://hdl.handle.net/10230/23227
dc.language.iso engca
dc.publisher BioMed Centralca
dc.relation.ispartof Genome Biology. 2014; 15: R57
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/282510ca
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/262055
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/261123
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/330133
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2008-00357
dc.rights © 2014 Friedländer 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 credited. 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.ca
dc.rights.accessRights info:eu-repo/semantics/openAccessca
dc.rights.uri http://creativecommons.org/licenses/by/2.0
dc.subject.other RNA no missatgersca
dc.subject.other Genètica humanaca
dc.title Evidence for the biogenesis of more than 1,000 novel human microRNAsen
dc.type info:eu-repo/semantics/articleca
dc.type.version info:eu-repo/semantics/publishedVersionca

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