Tex19 paralogs are new members of the piRNA pathway controlling retrotransposon suppression

Tex19 genes are mammalian specific and duplicated to give Tex19.1 and Tex19.2 in some species, such as the mouse and rat. It has been demonstrated that mutant Tex19.1 males display a variable degree of infertility whereas they all upregulate MMERVK10C transposons in their germ line. In order to study the function of both paralogs in the mouse, we generated and studied Tex19 double knockout (Tex19DKO) mutant mice. Adult Tex19DKO males exhibited a fully penetrant phenotype, similar to the most severe phenotype observed in the single Tex19.1KO mice, with small testes and impaired spermatogenesis, defects in meiotic chromosome synapsis, persistence of DNA double-strand breaks during meiosis, lack of post-meiotic germ cells and upregulation of MMERVK10C expression. The phenotypic similarities to mice with knockouts in the Piwi family genes prompted us to check and then demonstrate, by immunoprecipitation and GST pulldown followed by mass spectrometry analyses, that TEX19 paralogs interact with PIWI proteins and the TEX19 VPTEL domain directly binds Piwi-interacting RNAs (piRNAs) in adult testes. We therefore identified two new members of the postnatal piRNA pathway.