title: The TDRD9-MIWI2 complex is essential for piRNA-mediated retrotransposon silencing in the mouse male germline.
abstract: Host-defense mechanisms against transposable elements are critical to protect the genome information. Here we show that tudor-domain containing 9 (Tdrd9) is essential for silencing Line-1 retrotransposon in the mouse male germline. Tdrd9 encodes an ATPase/DExH-type helicase, and its mutation causes male sterility showing meiotic failure. In Tdrd9 mutants, Line-1 was highly activated and piwi-interacting small RNAs (piRNAs) corresponding to Line-1 were increased, suggesting that feedforward amplification operates in the mutant. In fetal testes, Tdrd9 mutation causes Line-1 desilencing and an aberrant piRNA profile in prospermatogonia, followed by cognate DNA demethylation. TDRD9 complexes with MIWI2 with distinct compartmentalization in processing bodies, and this TDRD9-MIWI2 localization is regulated by MILI and TDRD1 residing at intermitochondrial cement. Our results identify TDRD9 as a functional partner of MIWI2 and indicate that the tudor-piwi association is a conserved feature, while two separate axes, TDRD9-MIWI2 and TDRD1-MILI, cooperate nonredundantly in the piwi-small RNA pathway in the mouse male germline.
authors.affiliation: Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Shoji
authors.forename: Takashi
authors.initials: T
authors.lastname: Tanaka
authors.forename: Mihoko
authors.initials: M
authors.lastname: Hosokawa
authors.forename: Michael
authors.initials: M
authors.lastname: Reuter
authors.forename: Alexander
authors.initials: A
authors.lastname: Stark
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Kato
authors.forename: Gen
authors.initials: G
authors.lastname: Kondoh
authors.forename: Katsuya
authors.initials: K
authors.lastname: Okawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Chujo
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Suzuki
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Hata
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Martin
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Noce
authors.forename: Satomi
authors.initials: S
authors.lastname: Kuramochi-Miyagawa
authors.forename: Toru
authors.initials: T
authors.lastname: Nakano
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sasaki
authors.forename: Ramesh S
authors.initials: RS
authors.lastname: Pillai
authors.forename: Norio
authors.initials: N
authors.lastname: Nakatsuji
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Chuma
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D060565:Argonaute Proteins; D023902:Chromosome Pairing; D004265:DNA Helicases / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D007248:Infertility, Male / Q000378:metabolism; D020084:Long Interspersed Nucleotide Elements; D008297:Male; D008540:Meiosis; D051379:Mice; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D013090:Spermatocytes / Q000378:metabolism*
chemical_list: D060565:Argonaute Proteins; C546575:PIWIL4 protein, mouse; C448521:Piwil2 protein, mouse; D011506:Proteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C546574:TDRD9 protein, mouse; D004265:DNA Helicases