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PMID:20059948

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Citation

Shoji, M, Tanaka, T, Hosokawa, M, Reuter, M, Stark, A, Kato, Y, Kondoh, G, Okawa, K, Chujo, T, Suzuki, T, Hata, K, Martin, SL, Noce, T, Kuramochi-Miyagawa, S, Nakano, T, Sasaki, H, Pillai, RS, Nakatsuji, N and Chuma, S (2009) The TDRD9-MIWI2 complex is essential for piRNA-mediated retrotransposon silencing in the mouse male germline. Dev. Cell 17:775-87

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.

Links

PubMed Online version:10.1016/j.devcel.2009.10.012

Keywords

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

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:TDRD9

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q8CGT6

F

Seeded From UniProt

complete

MOUSE:TDRD9

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:TDRD9

involved_in

GO:0007283: spermatogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:TDRD9

involved_in

GO:0007140: male meiotic nuclear division

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:TDRD9

located_in

GO:0071547: piP-body

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:TDRD9

involved_in

GO:0009566: fertilization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:TDRD9

involved_in

GO:0043046: DNA methylation involved in gamete generation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:TDRD9

involved_in

GO:0034587: piRNA metabolic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PIWL2

located_in

GO:0071546: pi-body

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:PIWL4

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q14BI7

F

Seeded From UniProt

complete

MOUSE:PIWL4

located_in

GO:0071547: piP-body

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:TDRD1

located_in

GO:0071546: pi-body

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:TDRD1

part_of

GO:0071546: pi-body

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:PIWL2

part_of

GO:0071546: pi-body

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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