Tudor domain containing 7 (Tdrd7) is essential for dynamic ribonucleoprotein (RNP) remodeling of chromatoid bodies during spermatogenesis
Tudor domain containing 7 (Tdrd7) is essential for dynamic ribonucleoprotein (RNP) remodeling of chromatoid bodies during spermatogenesis
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DOI：
10.1073/pnas.1015447108
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发表时间：
2011-06-28
影响因子：
11.1
通讯作者：
Chuma, Shinichiro
中科院分区：
文献类型：
--
作者：
Tanaka, Takashi;Hosokawa, Mihoko;Chuma, Shinichiro
在哺乳动物的雄性生殖系中，类染色体，细胞质核糖核蛋白（RNP）的专门组装，在减数分裂和单倍体发生过程中结构明显，但其发育起源和调控仍然难以捉摸。含有tudor结构域的蛋白质构成一类保守的类染色体体组分。我们发现，都铎结构域包含7（Tdrd 7），其中的缺陷导致男性不育和年龄相关性白内障（以及青光眼），是必不可少的单倍体精子细胞的发展和定义，在音乐会与Tdrd 6，关键的生物发生过程的拟染色体体。Tdrd 7和Tdrd 6的单敲除和双敲除表明，这些生精tudor基因协调了发育程序，用于有序重塑拟染色体体，包括最初的建立，随后的RNP与普遍存在的加工体/GW体融合以及后来的结构维持。Tdrd 7抑制LINE 1反转录转座子独立于其中Tdrd 1和Tdrd 9起作用的piwi相互作用RNA（皮尔纳）生物发生，表明不同的Tdrd途径作用于雄性生殖系中的反转录转座子。tdrd 6，相反，不影响反转录转座子，但在精子发生的后期，当类染色体体表现出侵略样的属性功能。我们的研究结果描绘，拟染色体体组装作为一个综合的隔间，结合生殖细胞和无处不在的功能，精子发生的进展，保守的都铎家族基因作为主调节器的这种独特的RNP重塑，这是遗传上的雄性生殖细胞系的完整性在哺乳动物。
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.