The TDRD9-MIWI2 complex is essential for piRNA-mediated retrotransposon silencing in the mouse male germline.
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.
Shoji
Masanobu
M
Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
Tanaka
Takashi
T
Hosokawa
Mihoko
M
Reuter
Michael
M
Stark
Alexander
A
Kato
Yuzuru
Y
Kondoh
Gen
G
Okawa
Katsuya
K
Chujo
Takeshi
T
Suzuki
Tsutomu
T
Hata
Kenichiro
K
Martin
Sandra L
SL
Noce
Toshiaki
T
Kuramochi-Miyagawa
Satomi
S
Nakano
Toru
T
Sasaki
Hiroyuki
H
Pillai
Ramesh S
RS
Nakatsuji
Norio
N
Chuma
Shinichiro
S
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*
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