title: DGCR8 Acts as an Adaptor for the Exosome Complex to Degrade Double-Stranded Structured RNAs.
abstract: The Microprocessor complex (DGCR8/Drosha) is required for microRNA (miRNA) biogenesis but also binds and regulates the stability of several types of cellular RNAs. Of particular interest, DGCR8 controls the stability of mature small nucleolar RNA (snoRNA) transcripts independently of Drosha, suggesting the existence of alternative DGCR8 complex(es) with other nucleases to process a variety of cellular RNAs. Here, we found that DGCR8 copurifies with subunits of the nuclear exosome, preferentially associating with its hRRP6-containing nucleolar form. Importantly, we demonstrate that DGCR8 is essential for the recruitment of the exosome to snoRNAs and to human telomerase RNA. In addition, we show that the DGCR8/exosome complex controls the stability of the human telomerase RNA component (hTR/TERC). Altogether, these data suggest that DGCR8 acts as an adaptor to recruit the exosome complex to structured RNAs and induce their degradation.
authors.affiliation: Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK.
authors.forename: Sara
authors.initials: S
authors.lastname: Macias
authors.affiliation: Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK.
authors.forename: Ross A
authors.initials: RA
authors.lastname: Cordiner
authors.affiliation: Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK.
authors.forename: Philippe
authors.initials: P
authors.lastname: Gautier
authors.affiliation: Department of Biology, Center for Computational and Applied Transcriptomics, University of Copenhagen, Ole Maaloes Vej 5, 2200 Copenhagen, Denmark.
authors.forename: Mireya
authors.initials: M
authors.lastname: Plass
authors.affiliation: Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK. Electronic address: javier.caceres@igmm.ed.ac.uk.
authors.forename: Javier F
authors.initials: JF
authors.lastname: Cáceres
mesh_terms: D000818:Animals; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D005095:Exoribonucleases / Q000378:metabolism*; D063326:Exosome Multienzyme Ribonuclease Complex / Q000378:metabolism*; D055354:Exosomes / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D020871:RNA Stability; D012330:RNA, Double-Stranded / Q000737:chemistry / Q000378:metabolism*; D020537:RNA, Small Nucleolar / Q000378:metabolism; D012343:RNA, Transfer / Q000737:chemistry* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*
chemical_list: C474043:DGCR8 protein, human; D012330:RNA, Double-Stranded; D020537:RNA, Small Nucleolar; D016601:RNA-Binding Proteins; D012343:RNA, Transfer; D005095:Exoribonucleases; D063326:Exosome Multienzyme Ribonuclease Complex; C077044:EXOSC10 protein, human