Abstract
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.
Highlights
The subfertility and chromosome mis-segregation in maternal aged oocytes has emerged as a serious globe health concern[1,2,3]
After germinal vesicle breakdown (GVBD), SENP3 accumulated around the chromosome region and co-localized with α -tubulin at the spindles in pre-metaphase I (MI) and MI stage of oocytes; during chromosome separation at anaphase I-telophase I (ATI) stage, SENP3 localized between the separating chromosomes and the minus end of spindle microtubules
The results showed that knockdown of SENP3 severely compromised polar body extrusion (PBI) ejection by disrupting γ -tubulin organization and spindle morphogenesis in mouse oocytes
Summary
The subfertility and chromosome mis-segregation in maternal aged oocytes has emerged as a serious globe health concern[1,2,3]. Mammals expresses six SENPs (SENP1-3 and SENP5-7)[18], those of which are liberated to varieties of roles including cohesion maintenance, spindle assembly and embryonic development[19,20,21,22] Among these SENPs, SENP3 tends to localize in nucleolus, and preferentialiy mediates SUMO-2/3 maturation and its removal from substrate[17,23,24]. We are trying to decipher how reduction in SENP3 native expression level affects meiotic progression This entitles us to identify a novel function of SENP3 in cell-cycle timing and spindle morphogenesis that broadens SENP3’s function beyond ribosome biogenesis in mitotic cells and defines SENP3 as a determinant of meiosis in mammal oocytes
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