title: piRNA-triggered MIWI ubiquitination and removal by APC/C in late spermatogenesis.
abstract: 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.
authors: 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.
authors: Shuang
authors: S
authors: Zhao
authors: Lan-Tao
authors: LT
authors: Gou
authors: Man
authors: M
authors: Zhang
authors: Li-Dong
authors: LD
authors: Zu
authors: Min-Min
authors: MM
authors: Hua
authors: Ye
authors: Y
authors: Hua
authors: Hui-Juan
authors: HJ
authors: Shi
authors: Yong
authors: Y
authors: Li
authors: Jinsong
authors: J
authors: Li
authors: Dangsheng
authors: D
authors: Li
authors: En-Duo
authors: ED
authors: Wang
authors: Mo-Fang
authors: MF
authors: Liu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D060565:Argonaute Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D005854:Germ Cells / Q000166:cytology / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013091:Spermatogenesis / Q000502:physiology*; D013737:Testis / Q000166:cytology / Q000502:physiology; D054875:Ubiquitination
chemical_list: D060565:Argonaute Proteins; C448522:Piwil1 protein, mouse; D012333:RNA, Messenger; D034741:RNA, Small Interfering