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dc.contributor.authorWu, Connie
dc.contributor.authorSo, Jessica
dc.contributor.authorDavis-Dusenbery, Brandi N.
dc.contributor.authorQi, Hank H.
dc.contributor.authorBloch, Donald B.
dc.contributor.authorShi, Yang
dc.contributor.authorLagna, Giorgio
dc.contributor.authorHata, Akiko
dc.date.accessioned2019-10-17T05:19:04Z
dc.date.issued2011
dc.identifier.citationWu, C., J. So, B. N. Davis-Dusenbery, H. H. Qi, D. B. Bloch, Y. Shi, G. Lagna, and A. Hata. 2011. “Hypoxia Potentiates MicroRNA-Mediated Gene Silencing through Posttranslational Modification of Argonaute2.” Molecular and Cellular Biology 31 (23): 4760–74. https://doi.org/10.1128/mcb.05776-11.
dc.identifier.issn0270-7306
dc.identifier.issn1067-8824
dc.identifier.issn1098-5549
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41555768*
dc.description.abstractHypoxia contributes to the pathogenesis of various human diseases, including pulmonary artery hypertension (PAH), stroke, myocardial or cerebral infarction, and cancer. For example, acute hypoxia causes selective pulmonary artery (PA) constriction and elevation of pulmonary artery pressure. Chronic hypoxia induces structural and functional changes to the pulmonary vasculature, which resembles the phenotype of human PAH and is commonly used as an animal model of this disease. The mechanisms that lead to hypoxia-induced phenotypic changes have not been fully elucidated. Here, we show that hypoxia increases type I collagen prolyl-4-hydroxylase [C-P4H(I)], which leads to prolyl-hydroxylation and accumulation of Argonaute2 (Ago2), a critical component of the RNA-induced silencing complex (RISC). Hydroxylation of Ago2 is required for the association of Ago2 with heat shock protein 90 (Hsp90), which is necessary for the loading of microRNAs (miRNAs) into the RISC, and translocation to stress granules (SGs). We demonstrate that hydroxylation of Ago2 increases the level of miRNAs and increases the endonuclease activity of Ago2. In summary, this study identifies hypoxia as a mediator of the miRNA-dependent gene silencing pathway through posttranslational modification of Ago2, which might be responsible for cell survival or pathological responses under low oxygen stress.
dc.language.isoen_US
dc.publisherAmerican Society for Microbiology
dash.licenseLAA
dc.titleHypoxia Potentiates MicroRNA-Mediated Gene Silencing through Posttranslational Modification of Argonaute2
dc.typeJournal Article
dc.description.versionVersion of Record
dc.relation.journalMolecular and Cellular Biology
dash.depositing.authorBloch, Donald B.::d6e81c79e2b5a07d97c85ebcf0a58059::600
dc.date.available2019-10-17T05:19:04Z
dash.workflow.comments1Science Serial ID 64447
dc.identifier.doi10.1128/MCB.05776-11
dash.source.volume31;23
dash.source.page4760


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