The TDRD9-MIWI2 Complex Is Essential for piRNA-Mediated Retrotransposon Silencing in the Mouse Male Germline

Masanobu Shoji, Takashi Tanaka, Mihoko Hosokawa, Michael Reuter, Alexander Stark, Yuzuru Kato, Gen Kondoh, Katsuya Okawa, Takeshi Chujo, Tsutomu Suzuki, Kenichiro Hata, Sandra L. Martin, Toshiaki Noce, Satomi Kuramochi-Miyagawa, Toru Nakano, Hiroyuki Sasaki, Ramesh S. Pillai, Norio Nakatsuji, Shinichiro Chuma

Research output: Contribution to journalArticlepeer-review

254 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)775-787
Number of pages13
JournalDevelopmental Cell
Issue number6
Publication statusPublished - Dec 15 2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • General Biochemistry,Genetics and Molecular Biology
  • Developmental Biology
  • Cell Biology


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