Department of Anatomy and Cell Biology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
J Cell Biol. 2011 Mar 7;192(5):781-95. doi: 10.1083/jcb.201009043.
The Tudor domain-containing proteins (TDRDs) are an evolutionarily conserved family of proteins involved in germ cell development. We show here that in mice, TDRD5 is a novel component of the intermitochondrial cements (IMCs) and the chromatoid bodies (CBs), which are cytoplasmic ribonucleoprotein granules involved in RNA processing for spermatogenesis. Tdrd5-deficient males are sterile because of spermiogenic arrest at the round spermatid stage, with occasional failure in meiotic prophase. Without TDRD5, IMCs and CBs are disorganized, with mislocalization of their key components, including TDRD1/6/7/9 and MIWI/MILI/MIWI2. In addition, Tdrd5-deficient germ cells fail to repress LINE-1 retrotransposons with DNA-demethylated promoters. Cyclic adenosine monophosphate response element modulator (CREM) and TRF2, key transcription factors for spermiogenesis, are expressed in Tdrd5-deficient round spermatids, but their targets, including Prm1/Prm2/Tnp1, are severely down-regulated, which indicates the importance of IMC/CB-mediated regulation for postmeiotic gene expression. Strikingly, Tdrd5-deficient round spermatids injected into oocytes contribute to fertile offspring, demonstrating that acquisition of a functional haploid genome may be uncoupled from TDRD5 function.
Tudor 结构域蛋白（TDRDs）是一个进化上保守的蛋白家族，参与生殖细胞的发育。我们在这里表明，在小鼠中，TDRD5 是线粒体间连接体（IMCs）和染色质小体（CBs）的一个新组成部分，IMCs 和 CBs 是参与精子发生的 RNA 加工的细胞质核糖核蛋白颗粒。由于精子发生阻滞在圆形精子细胞阶段，减数分裂前期偶尔失败，Tdrd5 缺陷型雄性不育。没有 TDRD5，IMCs 和 CBs 就会出现紊乱，其关键成分（包括 TDRD1/6/7/9 和 MIWI/MILI/MIWI2）发生定位错误。此外，缺乏 TDRD5 的生殖细胞无法抑制启动子去甲基化的 LINE-1 反转录转座子。环磷酸腺苷反应元件调节因子（CREM）和 TRF2 是精子发生的关键转录因子，在 Tdrd5 缺陷的圆形精子细胞中表达，但它们的靶基因，包括 Prm1/Prm2/Tnp1，严重下调，这表明 IMC/CB 介导的调节对减数后基因表达的重要性。引人注目的是，注入卵母细胞的 Tdrd5 缺陷型圆形精子细胞有助于产生可育的后代，这表明获得功能性单倍体基因组可能与 TDRD5 功能无关。
