Tudor domain containing 12 (TDRD12) is essential for secondary PIWI interacting RNA biogenesis in mice

Proc Natl Acad Sci U S A. 2013 Oct 8;110(41):16492-7. doi: 10.1073/pnas.1316316110. Epub 2013 Sep 25.


Piwi-interacting RNAs (piRNAs) are gonad-specific small RNAs that provide defense against transposable genetic elements called transposons. Our knowledge of piRNA biogenesis is sketchy, partly due to an incomplete inventory of the factors involved. Here, we identify Tudor domain-containing 12 (TDRD12; also known as ECAT8) as a unique piRNA biogenesis factor in mice. TDRD12 is detected in complexes containing Piwi protein MILI (PIWIL2), its associated primary piRNAs, and TDRD1, all of which are already implicated in secondary piRNA biogenesis. Male mice carrying either a nonsense point mutation (reproductive mutant 23 or repro23 mice) or a targeted deletion in the Tdrd12 locus are infertile and derepress retrotransposons. We find that TDRD12 is dispensable for primary piRNA biogenesis but essential for production of secondary piRNAs that enter Piwi protein MIWI2 (PIWIL4). Cell-culture studies with the insect ortholog of TDRD12 suggest a role for the multidomain protein in mediating complex formation with other participants during secondary piRNA biogenesis.

Keywords: DNA methylation; helicase; spermatogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Blotting, Northern
  • Bombyx
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism*
  • Cloning, Molecular
  • Computational Biology
  • DNA Methylation / physiology*
  • DNA Primers / genetics
  • DNA Transposable Elements / genetics
  • DNA Transposable Elements / physiology*
  • DNA, Complementary / genetics
  • Fluorescent Antibody Technique
  • Genetic Vectors / genetics
  • Germ Cells / physiology*
  • Immunoprecipitation
  • Male
  • Mice
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • RNA, Small Interfering / biosynthesis*
  • RNA-Induced Silencing Complex / genetics
  • RNA-Induced Silencing Complex / physiology*


  • Carrier Proteins
  • DNA Primers
  • DNA Transposable Elements
  • DNA, Complementary
  • RNA, Small Interfering
  • RNA-Induced Silencing Complex
  • tudor domain-containing protein 12, mouse

Associated data

  • GEO/GSE50544