title: UAP56 couples piRNA clusters to the perinuclear transposon silencing machinery.
abstract: 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.
authors.affiliation: Program in Cell and Developmental Dynamics, University of Massachusetts Medical School, Worcester, MA 01655, USA; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.affiliation: Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors.forename: Jia
authors.initials: J
authors.lastname: Xu
authors.affiliation: Program in Cell and Developmental Dynamics, University of Massachusetts Medical School, Worcester, MA 01655, USA; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Program in Cell and Developmental Dynamics, University of Massachusetts Medical School, Worcester, MA 01655, USA; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors.forename: Birgit S
authors.initials: BS
authors.lastname: Koppetsch
authors.affiliation: Program in Cell and Developmental Dynamics, University of Massachusetts Medical School, Worcester, MA 01655, USA; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors.forename: Nadine
authors.initials: N
authors.lastname: Schultz
authors.affiliation: Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors.forename: Thom
authors.initials: T
authors.lastname: Vreven
authors.affiliation: Centre National de la Recherche Scientifique, Unité Propre de Recherche 9022, Institut de Biologie Moléculaire et Cellulaire, Université de Strasbourg, 67 084 Strasbourg Cedex, France.
authors.forename: Carine
authors.initials: C
authors.lastname: Meignin
authors.affiliation: Department of Biochemistry, The University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Ilan
authors.initials: I
authors.lastname: Davis
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01655, USA; Howard Hughes Medical Institute.
authors.forename: Phillip D
authors.initials: PD
authors.lastname: Zamore
authors.affiliation: Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA 01655, USA. Electronic address: zhiping.weng@umassmed.edu.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Weng
authors.affiliation: Program in Cell and Developmental Dynamics, University of Massachusetts Medical School, Worcester, MA 01655, USA; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA. Electronic address: william.theurkauf@umassmed.edu.
authors.forename: William E
authors.initials: WE
authors.lastname: Theurkauf
mesh_terms: D000818:Animals; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D004249:DNA Damage; D004251:DNA Transposable Elements; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism*; D005260:Female; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism*; D008297:Male; D009685:Nuclear Envelope / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism*
chemical_list: D004251:DNA Transposable Elements; D029721:Drosophila Proteins; D034741:RNA, Small Interfering; C107854:Hel25E protein, Drosophila; C088269:vas protein, Drosophila; D053487:DEAD-box RNA Helicases