title: Vigilins bind to promiscuously A-to-I-edited RNAs and are involved in the formation of heterochromatin.
abstract: The fate of double-stranded RNA (dsRNA) in the cell depends on both its length and location . The expression of dsRNA in the nucleus leads to several distinct consequences. First, the promiscuous deamination of adenosines to inosines by dsRNA-specific adenosine deaminase (ADAR) can lead to the nuclear retention of edited transcripts . Second, dsRNAs might induce heterochromatic gene silencing through an RNAi-related mechanism . Is RNA editing also connected to heterochromatin? We report that members of the conserved Vigilin class of proteins have a high affinity for inosine-containing RNAs. In agreement with other work , we find that these proteins localize to heterochromatin and that mutation or depletion of the Drosophila Vigilin, DDP1, leads to altered nuclear morphology and defects in heterochromatin and chromosome segregation. Furthermore, nuclear Vigilin is found in complexes containing not only the editing enzyme ADAR1 but also RNA helicase A and Ku86/70. In the presence of RNA, the Vigilin complex recruits the DNA-PKcs enzyme, which appears to phosphorylate a discrete set of targets, some or all of which are known to participate in chromatin silencing. These results are consistent with a mechanistic link between components of the DNA-repair machinery and RNA-mediated gene silencing.
authors.affiliation: Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, CT 06030 USA.
authors.forename: Qiaoqiao
authors.initials: Q
authors.lastname: Wang
authors.forename: Zuo
authors.initials: Z
authors.lastname: Zhang
authors.forename: Katherine
authors.initials: K
authors.lastname: Blackwell
authors.forename: Gordon G
authors.initials: GG
authors.lastname: Carmichael
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D017931:DNA Primers; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism; D005434:Flow Cytometry; D020868:Gene Silencing; D006367:HeLa Cells; D006570:Heterochromatin / Q000378:metabolism*; D006801:Humans; D007288:Inosine / Q000378:metabolism*; D013058:Mass Spectrometry; D009687:Nuclear Proteins / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D012330:RNA, Double-Stranded / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; C491076:Dp1 protein, Drosophila; D029721:Drosophila Proteins; D006570:Heterochromatin; D009687:Nuclear Proteins; D012330:RNA, Double-Stranded; D016601:RNA-Binding Proteins; C075197:high density lipoprotein binding protein; D007288:Inosine