UAP56 couples piRNA clusters to the perinuclear transposon silencing machinery
Department of Biochemistry and Molecular Pharmacology; Program in Bioinformatics and Integrative Biology; Program in Molecular Medicine; Program in Cell and Developmental Dynamics
Medical Subject Headings
Animals; DEAD-box RNA Helicases; DNA Damage; DNA Transposable Elements; Drosophila Proteins; Drosophila melanogaster; Female; Germ Cells; Male; Nuclear Envelope; RNA, Small Interfering
Bioinformatics | Computational Biology | Genetics and Genomics
piRNAs silence transposons during germline development. In Drosophila, transcripts from heterochromatic clusters are processed into primary piRNAs in the perinuclear nuage. The nuclear DEAD box protein UAP56 has been previously implicated in mRNA splicing and export, whereas the DEAD box protein Vasa has an established role in piRNA production and localizes to nuage with the piRNA binding PIWI proteins Ago3 and Aub. We show that UAP56 colocalizes with the cluster-associated HP1 variant Rhino, that nuage granules containing Vasa localize directly across the nuclear envelope from cluster foci containing UAP56 and Rhino, and that cluster transcripts immunoprecipitate with both Vasa and UAP56. Significantly, a charge-substitution mutation that alters a conserved surface residue in UAP56 disrupts colocalization with Rhino, germline piRNA production, transposon silencing, and perinuclear localization of Vasa. We therefore propose that UAP56 and Vasa function in a piRNA-processing compartment that spans the nuclear envelope.
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Citation: Cell. 2012 Nov 9;151(4):871-84. doi: 10.1016/j.cell.2012.09.040. Link to article on publisher's site
Zhang, Fan; Wang, Jie; Xu, Jia; Zhang, Zhao; Koppetsch, Birgit S.; Schultz, Nadine; Vreven, Thom; Meignin, Carine; Davis, Ilan; Zamore, Phillip D.; Weng, Zhiping; and Theurkauf, William E., "UAP56 couples piRNA clusters to the perinuclear transposon silencing machinery" (2012). Program in Bioinformatics and Integrative Biology Publications and Presentations. Paper 5.