The cohesin release factor Wapl interacts with Bub3 to govern SAC activity in female meiosis I

Zhou, Changyin; Miao, Yun; Cui, Zhaokang; ShiYang, Xiayan; Xiong, Bo

doi:10.1126/sciadv.aax3969

Cited by 9 publications

(10 citation statements)

References 43 publications

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“…Our previous study has reported that the role of WAPL in regulation of SAC activity in mouse oocytes is mediated by a pivotal component of SAC Bub3 [ 23 ]. To ask whether this mechanism is conserved in porcine oocytes, we assessed the expression and localization of BUB3 after WAPL depletion.…”

Section: Resultsmentioning

confidence: 99%

“…However, interestingly, in mammalian oocytes, homologous chromosomes become paired to form a bivalent in meiotic prophase [ 6 , 26 ], and subsequently the distal cohesins on bivalent arms are stripped by Separase instead of Wapl to allow homologous chromosome segregation at anaphase I stage [ 6 , 27 ]. In our recent study, we have unexpectedly found that Wapl functions as a SAC regulator by maintaining the stability of Bub3 to orchestrate the mouse oocyte meiotic progression [ 23 ]. Nevertheless, whether this noncanonal role of Wapl in oocyte meiosis is conserved among species still needs to be investigated.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, homozygous knockout of Wapl exhibits embryonic lethality in mice, suggesting that Wapl is indispensable for the mammalian embryonic development [ 22 ]. Interestingly, we have previously discovered a noncanonical role of Wapl in mediating SAC activity through maintenance of Bub3 stability during mouse oocyte meiosis I [ 23 ]. Here, we employed porcine oocytes as a model to investigate whether the unique function of WAPL beyond chromosome cohesion in oocyte meiosis is conserved among species.…”

Section: Introductionmentioning

confidence: 99%

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WAPL orchestrates porcine oocyte meiotic progression via control of spindle assembly checkpoint activity

Zhou

Miao

Zhang

et al. 2021

Reprod Biol Endocrinol

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Background In mitotic cells, WAPL acts as a cohesin release factor to remove cohesin complexes from chromosome arms during prophase to allow the accurate chromosome segregation in anaphase. However, we have recently documented that Wapl exerts a unique meiotic function in the spindle assembly checkpoint (SAC) control through maintaining Bub3 stability during mouse oocyte meiosis I. Whether this noncanonical function is conserved among species is still unknown. Methods We applied RNAi-based gene silencing approach to deplete WAPL in porcine oocytes, validating the conserved roles of WAPL in the regulation of SAC activity during mammalian oocyte maturation. We also employed immunostaining, immunoblotting and image quantification analyses to test the WAPL depletion on the meiotic progression, spindle assembly, chromosome alignment and dynamics of SAC protein in porcine oocytes. Results We showed that depletion of WAPL resulted in the accelerated meiotic progression by displaying the precocious polar body extrusion and compromised spindle assembly and chromosome alignment. Notably, we observed that the protein level of BUB3 was substantially reduced in WAPL-depleted oocytes, especially at kinetochores. Conclusions Collectively, our data demonstrate that WAPL participates in the porcine oocyte meiotic progression through maintenance of BUB3 protein levels and SAC activity. This meiotic function of WAPL in oocytes is highly conserved between pigs and mice.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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WAPL orchestrates porcine oocyte meiotic progression via control of spindle assembly checkpoint activity

Zhou

Miao

Zhang

et al. 2021

Reprod Biol Endocrinol

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“…Depletion of Bub3 also results in shorter metaphase I and metaphase II due to premature localization of protein phosphatase 1 (PP1) to kinetochores, which antagonizes Ipl1-mediated phosphorylation. A new role for the Bub1–Bub3 pathway in maintaining the balance between kinetochore localization of Ipl1 and PP1, a balance essential for accurate meiotic chromosome segregation and timely anaphase onset, has been proposed [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Aneuploid abortion correlates positively with MAD1 overexpression and miR-125b down-regulation

Zhao

Chen

et al. 2021

Mol Cytogenet

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Background Aneuploidy is the most frequent cause of early-embryo abortion. Any defect in chromosome segregation would fail to satisfy the spindle assembly checkpoint (SAC) during mitosis, halting metaphase and causing aneuploidy. The mitotic checkpoint complex (MCC), comprising MAD1, MAD2, Cdc20, BUBR1 and BUB3, plays a vital role in SAC activation. Studies have confirmed that overexpression of MAD2 and BUBR1 can facilitate correct chromosome segregation and embryo stability. Research also proves that miR-125b negatively regulates MAD1 expression by binding to its 3′UTR. However, miR-125b, Mad1 and Bub3 gene expression in aneuploid embryos of spontaneous abortion has not been reported to date. Methods In this study, embryonic villi from miscarried pregnancies were collected and divided into two groups (aneuploidy and euploidy) based on High-throughput ligation-dependent probe amplification (HLPA) and Fluorescence in situ hybridization (FISH) analyses. RNA levels of miR-125b, MAD1 and BUB3 were detected by Quantitative real-time PCR (qRT-PCR); protein levels of MAD1 and BUB3 were analysed by Western blotting. Results statistical analysis (p < 0.05) showed that miR-125b and BUB3 were significantly down-regulated in the aneuploidy group compared to the control group and that MAD1 was significantly up-regulated. Additionally, the MAD1 protein level was significantly higher in aneuploidy abortion villus, but BUB3 protein was only mildly increased. Correlation analysis revealed that expression of MAD1 correlated negatively with miR-125b. Conclusion These results suggest that aneuploid abortion correlates positively with MAD1 overexpression, which might be caused by insufficient levels of miR-125b. Taken together, our findings first confirmed the negative regulatory mode between MAD1 and miR-125b, providing a basis for further mechanism researches in aneuploid abortion.

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“…Two crucial regulators of cell cycle, cohesin and the SAC share common regulators to coordinate faithful chromosome segregation and orchestrate meiotic progression, Research show that cohesin release factor Wapl interacts with Bub3 to mediate the SAC function in oocyte meiosis I,Nevertheless,Wapl regulates Bub3 through an unknown way that requires further investigation 19 .Other research shows that ,in meiosis, Bub3 is crucial for correction of attachment errors. Depletion of Bub3 results in reduced levels of kinetochore-localized Ipl1 and concomitant massive chromosome missegregation caused by incorrect chromosome-spindle attachments.…”

Section: Discussionmentioning

confidence: 99%

Aneuploid Abortion Positively Correlate With MAD1 Overexpression and mir125b Depression

Zhao¹,

Li²,

Li³

et al. 2020

Preprint

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Background: Aneuploid is the most frequent cause of early embryo abortion, and any defect in chromosome segregation would fail to satisfy spindle assembly checkpoint (SAC) during mitosis, which could lead to the halted metaphase and aneuploid occurrence. Mitotic checkpoint complex(MCC), a complex compound of MAD1、MAD2、Cdc20、BUBR1 and BUB3, plays an important role in SAC activation. Studies have confirmed that the overexpression of MAD2 and BUBR1 can facilitate the correct chromosome segregation and embryo stability. Research identifications also proved that miR-125b negatively regulated MAD1 expression by binding to its 3’UTR. However, the expression of mir125b, MAD1 and BUB3 genes in aneuploidy embryos of spontaneous abortion has not been reported.Methods: In this study, embryonic villi from miscarriage pregnant women were collected and divided into two groups (aneuploidy and euploidy) by HLPA and FISH analysis. The RNA levels of mir125b, MAD1 and BUB3 were detected through QRT-PCR, while Western blot was further used to analyze the protein levels of MAD1 and BUB3.Results: SPSS 17.0 statistical analysis(P<0.05) showed that mir125b and BUB3 were significantly down-regulated in aneuploidy group compared to the control group, MAD1 was significantly up-regulated in RNA level; Additionally, MAD1 protein level was also significantly higher while BUB3 was mildly increased in aneuploidy abortion villus. Correlation analysis revealed that the expression of MAD1 was negatively correlated with Mir125b.Conclusion: these results suggested that aneuploid abortion was positively correlated with MAD1 overexpression which might be caused by insufficient mir125b.

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The cohesin release factor Wapl interacts with Bub3 to govern SAC activity in female meiosis I

Cited by 9 publications

References 43 publications

WAPL orchestrates porcine oocyte meiotic progression via control of spindle assembly checkpoint activity

WAPL orchestrates porcine oocyte meiotic progression via control of spindle assembly checkpoint activity

Aneuploid abortion correlates positively with MAD1 overexpression and miR-125b down-regulation

Aneuploid Abortion Positively Correlate With MAD1 Overexpression and mir125b Depression

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