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Título:
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A novel source for miR-21 expression through the alternative polyadenylation of VMP1 gene transcripts
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Autor/a:
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Ribas i Fortuny, Judit; Ni, Xiaohua; Castanares, Mark; Liu, Minzhi M.; Esopi, David; Yegnasubramanian, Srinivasan; Rodriguez, Ronald; Mendell, Joshua T.; Lupold, Shawn E.
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Notas:
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miR-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.
The ‘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. |
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Materia(s):
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-miR-21
-RNA
-Càncer
-Gens
-ADN
-Cicle cel·lular |
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Derechos:
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cc-by-nc, (c) Ribas et al., 2012
http://creativecommons.org/licenses/by-nc/3.0/es/deed.ca
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Tipo de documento:
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article
publishedVersion |
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Editor:
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Oxford University Press
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Compartir:
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