Yabuta et al. describe a Tudor family protein that controls multiple stages of sperm production.
Tudor domain–containing proteins (TDRDs) have several functions in germ cell development. Some family members prevent transposons from mobilizing and disrupting the germline genome during meiosis, whereas other TDRDs assemble the RNA protein granules that pack the germ cell cytoplasm and regulate the turnover and expression of mRNAs critical for spermatid maturation. Yabuta et al. found that one family member, TDRD5, is involved in both of these processes.
The LINE-1 retrotransposon was up-regulated in mouse testes lacking TDRD5, indicating that the protein works with other TDRD family members to repress transposon activation. High transposon expression can disrupt meiosis, but most germ cells lacking TDRD5 successfully formed haploid spermatids. Further development was blocked, however, as the immature sperm failed to express key maturation genes, probably because two types of RNA-processing granules, intermitochondrial cements and chromatoid bodies, were disrupted. As a result, male mice lacking TDRD5 were infertile. But their arrested spermatids could give rise to healthy offspring if they were directly injected into oocytes, suggesting that increased transposon activity doesn't damage the genome of TDRD5-null germ cells.
TDRDs work in conjunction with PIWI proteins and PIWI-interacting RNAs (piRNAs). Senior author Mitinori Saitou plans to investigate how TDRD5 represses transposons and regulates germ cell mRNAs by isolating its binding partners and examining how piRNA expression is altered in TDRD5's absence.