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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Tudor domain containing 7 (Tdrd7) is essential for dynamic ribonucleoprotein (RNP) remodeling of chromatoid bodies during spermatogenesis
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Tudor domain containing 7 (Tdrd7) is essential for dynamic ribonucleoprotein (RNP) remodeling of chromatoid bodies during spermatogenesis

机译:包含7(Tdrd7)的Tudor结构域对于精子发生过程中染色体体的动态核糖核蛋白(RNP)重塑至关重要

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摘要

In the male germline in mammals, chromatoid bodies, a specialized assembly of cytoplasmic ribonucleoprotein (RNP), are structurally evident during meiosis and haploidgenesis, but their developmental origin and regulation remain elusive. The tudor domain containing proteins constitute a conserved class of chromatoid body components. We show that tudor domain containing 7 (Tdrd7), the deficiency of which causes male sterility and age-related cataract (as well as glaucoma), is essential for haploid spermatid development ' and defines, in concert with Tdrd6, key biogenesis processes of chromatoid bodies. Single and double knockouts of Tdrd7 and Tdrd6 demonstrated that these spermiogenic tudor genes orchestrate developmental programs for ordered remodeling of chromatoid bodies, including the initial establishment, subsequent RNP fusion with ubiquitous processing bodies/GW bodies and later structural maintenance. Tdrd7 suppresses LINE1 retrotransposons independently of piwi-interacting RNA (piRNA) biogenesis wherein Tdrd1 and Tdrd9 operate, indicating that distinct Tdrd pathways act against retrotransposons in the male germline. Tdrd6, in contrast, does not affect retrotransposons but functions at a later stage of spermiogenesis when chromatoid bodies exhibit aggresome-like properties. Our results delineate that chromatoid bodies assemble as an integrated compartment incorporating both germline and ubiquitous features as spermatogenesis proceeds and that the conserved tudor family genes act as master regulators of this unique RNP remodeling, which is genetically linked to the male germline integrity in mammals.
机译:在减数分裂和单倍体发生过程中,在哺乳动物的雄性生殖系中,类染色体体是细胞质核糖核蛋白(RNP)的特殊组装,在结构上很明显,但它们的发育起源和调控仍然难以捉摸。包含tudor结构域的蛋白质构成了保守的类染色体体成分。我们显示包含7(Tdrd7)的都铎域,其缺乏导致男性不育和与年龄有关的白内障(以及青光眼),对于单倍体精子细胞发育是必不可少的',并且与Tdrd6共同定义了类染色体的关键生物发生过程身体。 Tdrd7和Tdrd6的单和双敲除表明这些生精的tudor基因编排了有序重塑类染色体体的发育程序,包括最初的建立,随后的RNP与无处不在的加工体/ GW体的融合以及后来的结构维护。 Tdrd7抑制LINE1逆转座子独立于piwi相互作用RNA(piRNA)生物发生,其中Tdrd1和Tdrd9起作用,表明不同的Tdrd途径对雄性种系中的逆转座子起作用。相反,Tdrd6不会影响反转录转座子,但在类染色体体表现出类似聚集体的特性时,在精子发生的后期起作用。我们的研究结果表明,随着精子发生,类染色体体组装成一个包含种系和普遍存在特征的整合区室,保守的都铎家族基因充当这种独特的RNP重塑的主要调控因子,后者与哺乳动物的雄性种系完整性遗传相关。

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    lnstitute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan;

    lnstitute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan,lnstitute for Integrated Cell-Material Sciences, Kyoto University, Kyoto 606-8501, Japan;

    Watson School of Biological Sciences, Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724;

    European Molecular Biology Laboratory, 38042 Grenoble Cedex 9, France;

    lnstitute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan;

    lnstitute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan;

    lnstitute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan;

    Chemicals Assessment Center, Chemicals Evaluation and Research Institute,Saitama 345-0043, Japan;

    lnstitute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan;

    Drug Discovery Research Laboratories, Kyowa Hakko Kirin, Nagaizumi 411-8731, Japan;

    Faculty of Frontier Biosciences and Medical School, Osaka University, Osaka 565-0871, Japan;

    Faculty of Frontier Biosciences and Medical School, Osaka University, Osaka 565-0871, Japan;

    Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY 10029;

    Watson School of Biological Sciences, Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724;

    European Molecular Biology Laboratory, 38042 Grenoble Cedex 9, France;

    lnstitute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan,lnstitute for Integrated Cell-Material Sciences, Kyoto University, Kyoto 606-8501, Japan;

    lnstitute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    germ cells; germinal granules; nuage;

    机译:生殖细胞;生发颗粒云;

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