title: Co-chaperone Hsp70/Hsp90-organizing protein (Hop) is required for transposon silencing and Piwi-interacting RNA (piRNA) biogenesis.
abstract: Piwi-interacting RNAs (piRNAs) are 26-30-nucleotide germ line-specific small non-coding RNAs that have evolutionarily conserved function in mobile genetic element (transposons) silencing and maintenance of genome integrity.DrosophilaHsp70/90-organizing protein homolog (Hop), a co-chaperone, interacts with piRNA-binding protein Piwi and mediates silencing of phenotypic variations. However, it is not known whether Hop has a direct role in piRNA biogenesis and transposon silencing. Here, we show that knockdown of Hop in the germ line nurse cells (GLKD) ofDrosophilaovaries leads to activation of transposons. Hop GLKD females can lay eggs at the same rate as wild-type counterparts, but the eggs do not hatch into larvae. Hop GLKD leads to the accumulation of γ-H2Av foci in the germ line, indicating increased DNA damage in the ovary. We also show that Hop GLKD-induced transposon up-regulation is due to inefficient piRNA biogenesis. Based on these results, we conclude that Hop is a critical component of the piRNA pathway and that it maintains genome integrity by silencing transposons.
authors.affiliation: From the Department of Biochemistry and Molecular Biology and Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina 29425 and.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Karam
authors.affiliation: From the Department of Biochemistry and Molecular Biology and Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina 29425 and.
authors.forename: Rasesh Y
authors.initials: RY
authors.lastname: Parikh
authors.affiliation: From the Department of Biochemistry and Molecular Biology and Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina 29425 and.
authors.forename: Dhananjaya
authors.initials: D
authors.lastname: Nayak
authors.affiliation: the Institute of Organismic and Molecular Evolutionary Biology, Johannes Gutenberg-Universität Mainz, 55122 Mainz, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Rosenkranz
authors.affiliation: From the Department of Biochemistry and Molecular Biology and Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina 29425 and gangaraj@musc.edu.
authors.forename: Vamsi K
authors.initials: VK
authors.lastname: Gangaraju
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics / Q000378:metabolism; D060565:Argonaute Proteins / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage; D004251:DNA Transposable Elements; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D005260:Female; D020868:Gene Silencing; D042822:Genomic Instability; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism*; D053612:Janus Kinases / Q000235:genetics / Q000378:metabolism*; D010053:Ovary / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000096:biosynthesis* / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D060565:Argonaute Proteins; D004251:DNA Transposable Elements; D029721:Drosophila Proteins; D034741:RNA, Small Interfering; D014157:Transcription Factors; C116498:piwi protein, Drosophila; D053612:Janus Kinases; C085845:hop protein, Drosophila
keywords: DNA damage response; RNA; RNA interference (RNAi); heat shock protein (HSP); heat shock protein 90 (Hsp90)