The SUMO Protease SENP3 Orchestrates G2-M Transition and Spindle Assembly in Mouse Oocytes.
Oocyte meiosis is a transcription quiescence process and the cell-cycle progression is coordinated by multiple post-translational modifications, including SUMOylation. SENP3 an important deSUMOylation protease has been intensively studied in ribosome biogenesis and oxidative stress. However, the roles of SENP3 in cell-cycle regulation remain enigmatic, particularly for oocyte meiotic maturation. Here, we found that SENP3 co-localized with spindles during oocyte meiosis and silencing of SENP3 severely compromised the M phase entry (germinal vesicle breakdown, GVBD) and first polar body extrusion (PBI). The failure in polar body extrusion was due to the dysfunction of γ-tubulin that caused defective spindle morphogenesis. SENP3 depletion led to mislocalization and a substantial loss of Aurora A (an essential protein for MTOCs localization and spindle dynamics) while irregularly dispersed distribution of Bora (a binding partner and activator of Aurora A) in cytoplasm instead of concentrating at spindles. The SUMO-2/3 but not SUMO-1 conjugates were globally decreased by SENP3 RNAi. Additionally, the spindle assembly checkpoint remained functional upon SENP3 RNAi. Our findings renew the picture of SENP3 function by exploring its role in meiosis resumption, spindle assembly and following polar body emission during mouse oocyte meiotic maturation, which is potentially due to its proteolytic activity that facilitate SUMO-2/3 maturation.
Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China.
Chun-Jie
CJ
Huang
Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China.
Di
D
Wu
Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China.
Faheem Ahmed
FA
Khan
Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China.
Li-Jun
LJ
Huo
D000818:Animals; D002455:Cell Division / Q000502:physiology*; D003546:Cysteine Endopeptidases; D016195:G2 Phase / Q000502:physiology*; D055785:Gene Knockdown Techniques; D051379:Mice; D009865:Oocytes / Q000166:cytology*; D010447:Peptide Hydrolases / Q000235:genetics / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D008941:Spindle Apparatus
D034741:RNA, Small Interfering; D010447:Peptide Hydrolases; D003546:Cysteine Endopeptidases; C492190:Senp3 protein, mouse