A novel source for miR-21 expression through the alternative polyadenylation of VMP1 gene transcripts

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dc.contributor.authorRibas i Fortuny, Judit
dc.contributor.authorNi, Xiaohua
dc.contributor.authorCastanares, Mark
dc.contributor.authorLiu, Minzhi M.
dc.contributor.authorEsopi, David
dc.contributor.authorYegnasubramanian, Srinivasan
dc.contributor.authorRodriguez, Ronald
dc.contributor.authorMendell, Joshua T.
dc.contributor.authorLupold, Shawn E.
dc.date.accessioned2012-12-11T11:22:06Z
dc.date.available2012-12-11T11:22:06Z
dc.date.issued2012
dc.description.abstractmiR-21 is the most commonly over-expressed microRNA (miRNA) in cancer and a proven oncogene. Hsa-miR-21 is located on chromosome 17q23.2, immediately downstream of the vacuole membrane protein-1 (VMP1) gene, also known as TMEM49. VMP1 transcripts initiate ∼130 kb upstream of miR-21, are spliced, and polyadenylated only a few hundred base pairs upstream of the miR-21 hairpin. On the other hand, primary miR-21 transcripts (pri-miR-21) originate within the last introns of VMP1, but bypass VMP1 polyadenylation signals to include the miR-21 hairpin. Here, we report that VMP1 transcripts can also bypass these polyadenylation signals to include miR-21, thus providing a novel and independently regulated source of miR-21, termed VMP1–miR-21. Northern blotting, gene-specific RT-PCR, RNA pull-down and DNA branching assays support that VMP1–miR-21 is expressed at significant levels in a number of cancer cell lines and that it is processed by the Microprocessor complex to produce mature miR-21. VMP1 and pri-miR-21 are induced by common stimuli, such as phorbol-12-myristate-13-acetate (PMA) and androgens, but show differential responses to some stimuli such as epigenetic modifying agents. Collectively, these results indicate that miR-21 is a unique miRNA capable of being regulated by alternative polyadenylation and two independent gene promoters.ca_ES
dc.description.sponsorshipThe ‘National Institutes of Health/National Cancer Institute’ [5R01CA143299 to S.E.L., 5P50CA058236 to S.E.L. (Project 1)]; Department of Defense Prostate Cancer Research Fund [W81XWH-08-13-5 to S.E.L.]; Patrick C. Walsh Prostate Cancer Research Fund (to S.E.L.); Spanish ‘Ministerio de Ciencia e Innovación’ [SAF2011-29730 to J.R.]. Funding for open access charge: National Institutes of Health/NCI R01CA143299.
dc.identifier.doihttps://doi.org/10.1093/nar/gks308
dc.identifier.idgrec017838
dc.identifier.issn0305-1048
dc.identifier.urihttp://hdl.handle.net/10459.1/46370
dc.language.isoengca_ES
dc.publisherOxford University Pressca_ES
dc.relationinfo:eu-repo/grantAgreement/MICINN//SAF2011-29730/ES/REGULACION DE LA AUTOFAGIA POR LOS GENES TMEM49 Y MIR-21/
dc.relation.isformatofReproducció del document publicat a: https://doi.org/10.1093/nar/gks308ca_ES
dc.relation.ispartofNucleic Acids Research, 2012, vol. 40, núm. 14, p. 6821-6833ca_ES
dc.rightscc-by-nc, (c) Ribas et al., 2012ca_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccessca_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc/3.0/es/deed.caca_ES
dc.subjectmiR-21ca_ES
dc.subject.otherRNAca_ES
dc.subject.otherCàncerca_ES
dc.subject.otherGensca_ES
dc.subject.otherADNca_ES
dc.subject.otherCicle cel·lularca_ES
dc.titleA novel source for miR-21 expression through the alternative polyadenylation of VMP1 gene transcriptsca_ES
dc.typearticleca_ES
dc.type.versionpublishedVersionca_ES
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