近日，中科院上海生命科学研究院的研究者在新研究中，揭示了piRNA在生殖细胞发育过程中调控MIWI/piRNA互做机制的重要的作用，对深入了解piRNA作用通路调控哺乳动物生殖功能具有重要意义，这一重大发现发表在近期的Cell子刊Developmental Cell杂志上。
piRNA是一类与PIWI蛋白相作用的小RNA，主要在生殖细胞系中表达。研究表明PIWI/piRNA作用机制在哺乳动物中沉默转座子，维持基因的完整性等方面均具有重要作用。中科院上海生命科学研究院的研究人员采用特异性人工合成piRNA mimic (RiboBio Co. Ltd.) ，应用到生殖细胞中的研究中，扩展了PIWI/piRNA机制的发生及其功能作用。研究人员发现小鼠精子成熟后期，PIWI（MIWI）通过APC/C-26S蛋白酶通路而被降解，piRNA在这一过程中起到至关重要的作用。在研究中，一个有趣的现象是，在晚期精细胞中piRNA触发的MIWI的破坏，从而导致了piRNA的自身的清除。这一现象揭示了在特定的发育阶段，调节清除MIWI/piRNA机制的前馈机制。重要的是，研究人员发现适当清除MIWI/piRNA机制是精子成熟的必要条件。这些结果表明piRNA通过泛素-蛋白酶体信号通路调控了MIWI/piRNA机制的清除，证实在雄性生殖细胞发育过程中适当的时序调控MIWI/piRNA具有非常重要的意义。
piRNA（Piwi-interactingRNA）是从哺乳动物生殖细胞中分离得到的一类长度约为30nt的小RNA，并且这种小RNA与PIWI蛋白家族成员相结合才能发挥它的调控作用。
piRNA-Triggered MIWI Ubiquitination and Removal by APC/C in Late Spermatogenesis.
Developmental Cell24, 13–25, January 14, 2013
Summary：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 understandin 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.