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RBM14调节小鼠卵母细胞减数分裂成熟过程中的微管蛋白乙酰化并调控纺锤体形态。

RBM14 Modulates Tubulin Acetylation and Regulates Spindle Morphology During Meiotic Maturation in Mouse Oocytes.

作者信息

Qin Hao, Qu Yi, Yuan Yi-Feng, Li Yang-Yang, Qiao Jie

机构信息

Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.

National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing, China.

出版信息

Front Cell Dev Biol. 2021 Feb 2;9:635728. doi: 10.3389/fcell.2021.635728. eCollection 2021.

Abstract

RBM14 is an RNA-binding protein that regulates spindle integrity in mitosis; however, its functions during meiosis are still unclear. In this study, we discovered that RBM14 expression was down-regulated in oocytes from old mice. The RBM14 distribution at different stages of meiosis was explored, while it presents overlapped localization patterns with α-tubulin in MI- and MII-stage oocytes. Treatment of MI-stage oocytes with spindle-perturbing agents revealed that RBM14 was co-localized with microtubules. RBM14 knockdown with RBM14-specific morpholino showed that RBM14-depleted oocytes underwent symmetric division compared to the controls. RBM14 knockdown also resulted in spindle defects and chromosome abnormalities during oocyte maturation, presumably due to α-tubulin hyperacetylation. Co-immunoprecipitation analysis demonstrated that RBM14 is interacted with endogenous α-tubulin in mammalian cells. These findings indicate that RBM14 is an essential modulator of oocyte meiotic maturation by regulating α-tubulin acetylation to affect spindle morphology and chromosome alignment. Consequently, RBM14 represents a potential biomarker of oocyte quality and a novel therapeutic target in women with oocyte maturation failure.

摘要

RBM14是一种RNA结合蛋白,可在有丝分裂过程中调节纺锤体完整性;然而,其在减数分裂过程中的功能仍不清楚。在本研究中,我们发现老年小鼠卵母细胞中RBM14的表达下调。我们探究了RBM14在减数分裂不同阶段的分布,发现它在MI期和MII期卵母细胞中与α-微管蛋白呈现重叠的定位模式。用纺锤体干扰剂处理MI期卵母细胞发现,RBM14与微管共定位。用RBM14特异性吗啉代寡核苷酸敲低RBM14表明,与对照组相比,RBM14缺失的卵母细胞进行对称分裂。RBM14敲低还导致卵母细胞成熟过程中纺锤体缺陷和染色体异常,这可能是由于α-微管蛋白过度乙酰化所致。免疫共沉淀分析表明,RBM14在哺乳动物细胞中与内源性α-微管蛋白相互作用。这些发现表明,RBM14通过调节α-微管蛋白乙酰化来影响纺锤体形态和染色体排列,是卵母细胞减数分裂成熟的重要调节因子。因此,RBM14是卵母细胞质量的潜在生物标志物,也是卵母细胞成熟失败女性的新型治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5148/7884444/1ab0833e59e6/fcell-09-635728-g0001.jpg

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