The TDRD9-MIWI2 complex is essential for piRNA-mediated retrotransposon silencing in the mouse male germline

Dev Cell. 2009 Dec;17(6):775-87. doi: 10.1016/j.devcel.2009.10.012.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Argonaute Proteins
  • Chromosome Pairing
  • DNA Helicases / chemistry
  • DNA Helicases / metabolism*
  • Female
  • Infertility, Male / metabolism
  • Long Interspersed Nucleotide Elements*
  • Male
  • Meiosis
  • Mice
  • Protein Structure, Tertiary
  • Proteins / metabolism
  • RNA, Small Interfering / metabolism*
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / metabolism*
  • Spermatocytes / metabolism*


  • Argonaute Proteins
  • PIWIL4 protein, mouse
  • Piwil2 protein, mouse
  • Proteins
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • TDRD9 protein, mouse
  • DNA Helicases