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The human box C/D snoRNA U3 is a miRNA source and miR-U3 regulates expression of sortin nexin 27

dc.contributor.authorLemus-Diaz, Nicolas
dc.contributor.authorFerreira, Rafael Rinaldi
dc.contributor.authorBohnsack, Katherine E
dc.contributor.authorGruber, Jens
dc.contributor.authorBohnsack, Markus T
dc.date.accessioned2020-07-31T15:30:01Z
dc.date.available2020-07-31T15:30:01Z
dc.date.issued2020de
dc.identifier.urihttp://resolver.sub.uni-goettingen.de/purl?gs-1/17489
dc.description.abstractMicroRNAs (miRNAs) are important regulators of eukaryotic gene expression and their dysfunction is often associated with cancer. Alongside the canonical miRNA biogenesis pathway involving stepwise processing and export of pri- and pre-miRNA transcripts by the microprocessor complex, Exportin 5 and Dicer, several alternative mechanisms of miRNA production have been described. Here, we reveal that the atypical box C/D snoRNA U3, which functions as a scaffold during early ribosome assembly, is a miRNA source. We show that a unique stem–loop structure in the 5′ domain of U3 is processed to form short RNA fragments that associate with Argonaute. miR-U3 production is independent of Drosha, and an increased amount of U3 in the cytoplasm in the absence of Dicer suggests that a portion of the full length snoRNA is exported to the cytoplasm where it is efficiently processed into miRNAs. Using reporter assays, we demonstrate that miR-U3 can act as a low proficiency miRNA in vivo and our data support the 3′ UTR of the sortin nexin SNX27 mRNA as an endogenous U3-derived miRNA target. We further reveal that perturbation of U3 snoRNP assembly induces miR-U3 production, highlighting potential cross-regulation of target mRNA expression and ribosome production.de
dc.description.sponsorshipOpen-Access-Publikationsfonds 2020
dc.language.isoengde
dc.rightsopenAccess
dc.rightsNamensnennung-Nicht-kommerziell 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/*
dc.subject.ddc610
dc.titleThe human box C/D snoRNA U3 is a miRNA source and miR-U3 regulates expression of sortin nexin 27de
dc.typejournalArticlede
dc.identifier.doi10.1093/nar/gkaa549
dc.type.versionpublishedVersionde
dc.relation.pISSN0305-1048
dc.relation.eISSN1362-4962
dc.bibliographicCitation.firstPage1de
dc.bibliographicCitation.lastPage16de
dc.type.subtypejournalArticle
dc.description.statuspeerReviewedde
dc.bibliographicCitation.journalNucleic Acids Researchde


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