State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Suzhou Municipal Hospital, Nanjing Medical University, Nanjing, China.
Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing, China.
Cell Death Differ. 2020 Aug;27(8):2468-2483. doi: 10.1038/s41418-020-0516-1. Epub 2020 Feb 24.
KIAA1429 (also known as vir-like mA methyltransferase-associated protein (VIRMA)), a newly identified component of the RNA mA methyltransferase complex, plays critical roles in guiding region-selective mA deposition. However, in mammals, whether KIAA1429 mediates RNA mA regulatory pathway functions in vivo remains unknown. Here, we show that the Kiaa1429-specific deficiency in oocytes resulted in female infertility with defective follicular development and fully grown germinal vesicle (GV) oocytes failing to undergo germinal vesicle breakdown (GVBD) and consequently losing the ability to resume meiosis. The oocyte growth is accompanied by the accumulation of abundant RNAs and posttranscriptional regulation. We found that the loss of Kiaa1429 could also lead to abnormal RNA metabolism in GV oocytes. RNA-seq profiling revealed that Kiaa1429 deletion altered the expression pattern of the oocyte-derived factors essential for follicular development. In addition, our data show that the conditional depletion of Kiaa1429 decreased the mA levels in oocytes and mainly affected the alternative splicing of genes associated with oogenesis. In summary, the mA methyltransferase KIAA1429-mediated RNA metabolism plays critical roles in folliculogenesis and the maintenance of oocyte competence.
KIAA1429(也称为类似病毒的 mA 甲基转移酶相关蛋白(VIRMA)),是 RNA mA 甲基转移酶复合物的新鉴定组成部分,在指导区域选择性 mA 沉积中发挥关键作用。然而,在哺乳动物中,KIAA1429 是否介导 RNA mA 调节途径的功能尚不清楚。在这里,我们表明卵母细胞中 KIAA1429 的特异性缺乏导致雌性不育,卵泡发育缺陷,完全成熟的生发泡(GV)卵母细胞无法进行生发泡破裂(GVBD),因此丧失了恢复减数分裂的能力。卵母细胞的生长伴随着大量 RNA 的积累和转录后调控。我们发现 Kiaa1429 的缺失也会导致 GV 卵母细胞中异常的 RNA 代谢。RNA-seq 分析显示,Kiaa1429 的缺失改变了卵泡发育所必需的卵母细胞来源因子的表达模式。此外,我们的数据表明,Kiaa1429 的条件性耗竭降低了卵母细胞中的 mA 水平,并且主要影响与卵母细胞发生相关的基因的可变剪接。总之,mA 甲基转移酶 KIAA1429 介导的 RNA 代谢在卵泡发生和卵母细胞能力的维持中发挥关键作用。