TDRD5 is required for retrotransposon silencing, chromatoid body assembly, and spermiogenesis in mice.
TDRD5 is required for retrotransposon silencing, chromatoid body assembly, and spermiogenesis in mice.
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DOI：
10.1083/jcb.201009043
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发表时间：
2011-03-07
期刊：
影响因子：
--
通讯作者：
Saitou M
中科院分区：
文献类型：
--
作者：
Yabuta Y;Ohta H;Abe T;Kurimoto K;Chuma S;Saitou M
尽管在圆形精子细胞阶段精子发生受阻，但tdrd 5缺陷小鼠仍发育出功能性单倍体基因组。含Tudor结构域蛋白（TDRD）是一个进化上保守的蛋白家族，参与生殖细胞发育。我们在这里表明，在小鼠中，TDRD 5是一个新的组成部分的线粒体水泥（IMC）和类染色体体（CB），这是细胞质核糖核蛋白颗粒参与RNA加工精子发生。tdrd 5缺陷的雄性不育，因为在圆形精子细胞阶段精子发生停滞，偶尔在减数分裂前期失败。如果没有TDRD 5，IMC和CB就会变得杂乱无章，其关键组件（包括TDRD 1/6/7/9和MIWI/MILI/MIWI 2）会出现定位错误。此外，Tdrd 5缺陷型生殖细胞不能用DNA去甲基化启动子抑制LINE-1反转录转座子。Tdrd 5缺陷的圆形精子细胞中，精子发生的关键转录因子环磷酸腺苷反应元件调节因子（CREM）和TRF 2表达，但其靶基因Prm 1/Prm 2/Tnp 1表达严重下调，表明IMC/CB介导的减数分裂后基因表达调控的重要性。引人注目的是，Tdrd 5缺陷的圆形精子细胞注入卵母细胞有助于生育后代，表明功能性单倍体基因组的获得可能与TDRD 5功能解偶联。
Tdrd5-deficient mice develop a functional haploid genome despite spermiogenesis arrest at the round spermatid stage. 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.
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影响因子：
4.1
作者：
Chuma, Shinichiro;Hosokawa, Mihoko;Nakatsuji, Norio
通讯作者：
Nakatsuji, Norio
影响因子：
3.5
作者：
Kato, Yuzuru;Kaneda, Masahiro;Sasaki, Hiroyuki
通讯作者：
Sasaki, Hiroyuki
影响因子：
64.8
作者：
Fimia, GM;De Cesare, D;Sassone-Corsi, P
通讯作者：
Sassone-Corsi, P
影响因子：
14.8
作者：
Kurimoto, Kazuki;Yabuta, Yukihiro;Saitou, Mitinori
通讯作者：
Saitou, Mitinori
影响因子：
64.5
作者：
BOSWELL, RE;MAHOWALD, AP
通讯作者：
MAHOWALD, AP