State Key Laboratory of Molecular Biology, Graduate University of Chinese Academy of Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Dev Cell. 2013 Jan 14;24(1):13-25. doi: 10.1016/j.devcel.2012.12.006.
The PIWI/PIWI-interacting RNA (piRNA) machinery has been well documented to maintain genome integrity by silencing transposons in animal germ cells. Recent studies have advanced our understanding of the biogenesis and function of this machinery; however, its metabolism has remained largely unexplored. Here, we show that murine PIWI (MIWI) is degraded through the APC/C-26S proteasome pathway and that piRNAs play an indispensable role in this process by enhancing MIWI interaction with an APC/C substrate-binding subunit. Interestingly, piRNA-triggered MIWI destruction occurs in late spermatids, which in turn leads to piRNA elimination, suggesting a feedforward mechanism for coordinated removal of the MIWI/piRNA machinery at a specific developmental stage. Importantly, the proper removal of MIWI/piRNA is essential for sperm maturation. Together, our results reveal a role for piRNAs in regulating the clearance of the MIWI/piRNA machinery via the ubiquitin-proteosome pathway and demonstrate the critical importance of proper temporal regulation of MIWI/piRNA in male germ cell development.
PIWI/PIWI 相互作用 RNA (piRNA) 机制通过沉默动物生殖细胞中转座子，已被充分证明可维持基因组完整性。最近的研究增进了我们对该机制生物发生和功能的理解；然而，其代谢仍在很大程度上未被探索。在这里，我们表明，鼠 PIWI (MIWI) 通过 APC/C-26S 蛋白酶体途径降解，并且 piRNA 通过增强 MIWI 与 APC/C 底物结合亚基的相互作用在该过程中发挥不可或缺的作用。有趣的是，piRNA 触发的 MIWI 破坏发生在晚期精母细胞中，这反过来又导致 piRNA 的消除，提示在特定发育阶段协调去除 MIWI/piRNA 机制的正反馈机制。重要的是，MIWI/piRNA 的适当去除对于精子成熟是必需的。总之，我们的结果揭示了 piRNA 通过泛素蛋白酶体途径调节 MIWI/piRNA 清除的作用，并证明了 MIWI/piRNA 在雄性生殖细胞发育中进行适当的时间调节的至关重要性。
