Pachytene piRNA biogenesis is a hallmark of the germline, distinct from another wave of pre-pachytene piRNA biogenesis with regard to the lack of a secondary amplification process known as the Ping-pong cycle. However, the underlying molecular mechanism and the venue for the suppression of the Ping-pong cycle remain elusive. Here, we showed that a testis-specific protein, ADAD2, interacts with a TDRD family member protein RNF17 and is associated with P-bodies. Importantly, ADAD2 directs RNF17 to repress Ping-pong activity in pachytene piRNA biogenesis. The P-body localization of RNF17 requires the intrinsically disordered domain of ADAD2. Deletion of Adad2 or Rnf17 causes the mislocalization of each other and subsequent Ping-pong activity derepression, secondary piRNAs overproduced, and disruption of P-body integrity at the meiotic stage, thereby leading to spermatogenesis arrested at the round spermatid stage. Collectively, by identifying the ADAD2-dependent mechanism, our study reveals a novel function of P-bodies in suppressing Ping-pong activity in pachytene piRNA biogenesis.

中文翻译：

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ADAD2 与 P 体中的 RNF17 相互作用，抑制粗线期 piRNA 生物发生中的乒乓循环

粗线期 piRNA 生物发生是种系的一个标志，与另一波前粗线期 piRNA 生物发生不同，它缺乏称为乒乓循环的二次扩增过程。然而，抑制乒乓循环的潜在分子机制和场所仍然难以捉摸。在这里，我们发现睾丸特异性蛋白 ADAD2 与 TDRD 家族成员蛋白 RNF17 相互作用，并与 P 体相关。重要的是，ADAD2 指导 RNF17 抑制粗线期 piRNA 生物发生中的乒乓球活性。 RNF17 的 P 体定位需要 ADAD2 本质上无序的结构域。 Adad2 或 Rnf17 的缺失会导致彼此的错误定位，进而导致乒乓球活动抑制、次级 piRNA 过量产生以及减数分裂阶段 P 体完整性的破坏，从而导致精子发生在圆形精子细胞阶段停滞。总的来说，通过识别 ADAD2 依赖性机制，我们的研究揭示了 P 体在抑制粗线期 piRNA 生物发生中的乒乓球活性方面的新功能。