Alternative splicing for germ cell‐specific <i>Mga</i> transcript can be eliminated without compromising mouse viability or fertility
Alternative splicing for germ cell‐specific <i>Mga</i> transcript can be eliminated without compromising mouse viability or fertility
复制标题
可以消除生殖细胞特异性 <i>Mga</i> 转录本的选择性剪接，而不会影响小鼠的活力或生育能力
DOI：
10.1111/dgd.12806
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Okuda Akihiko
中科院分区：
文献类型：
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作者：
Kitamura Yuka;Suzuki Ayumu;Uranishi Kousuke;Nishimoto Masazumi;Mizuno Seiya;Takahashi Satoru;Okuda Akihiko
视黄酸基因8（STRA 8）/MEIOSIN复合物和多梳阻遏复合物（PRC）1.6（PRC 1亚型）被认为分别是减数分裂起始的正调节因子和负调节因子。在减数分裂起始期间，PRC1.6的转录抑制活性必须减弱，以便减数分裂相关基因可以被STRA 8/MEIOSIN复合物有效激活。然而，控制PRC1.6功能受损的分子机制仍不清楚。我们最近证明，theMgagene，它编码PRC1.6的支架组件，产生变异mRNA的选择性剪接特异性减数分裂过程中。此外，异常的MGA蛋白编码的变体mRNA具有内在的能力，作为一个显性负调控对PRC1.6的建设，因此被认为是，至少部分地，参与损害的复杂。因此，为了明确评估Mgavariant mRNA产生在配子发生中的生理意义，我们检查了使小鼠不能产生Mgavariant mRNA的遗传操作的后果。我们的数据显示，突变小鼠在生存力和生育力方面与野生型小鼠相当。我们对精子发生的详细研究还表明，这种遗传改变与睾丸大小、生精周期、减数分裂开始时间或精原细胞和精母细胞标记基因表达的任何明显异常无关。总之，这些数据表明，生殖细胞特异性Mgavariant mRNA的产生不仅对生存力而且对配子发生都是不利的。
The stimulated by retinoic acid gene 8 (STRA8)/MEIOSIN complex and polycomb repressive complex (PRC) 1.6, a PRC1 subtype, are believed to be positive and negative regulators of meiotic onset, respectively. During meiotic initiation, the transcription repressive activity of PRC1.6 must be attenuated so that meiosis‐related genes can be effectively activated by the STRA8/MEIOSIN complex. However, the molecular mechanisms that control the impairment of PRC1.6 function remain unclear. We recently demonstrated that theMgagene, which encodes a scaffolding component of PRC1.6, produces variant mRNA by alternative splicing specifically during meiosis. Furthermore, the anomalous MGA protein encoded by the variant mRNA bears an intrinsic ability to function as a dominant negative regulator against the construction of PRC1.6 and is therefore assumed to be, at least in part, involved in impairment of the complex. Therefore, to unequivocally evaluate the physiological significance ofMgavariant mRNA production in gametogenesis, we examined the consequences of a genetic manipulation that renders mice unable to produceMgavariant mRNA. Our data revealed that mutant mice were equivalent to wild‐type mice in terms of viability and fertility. Our detailed examination of spermatogenesis also revealed that this genetic alteration is not associated with any apparent abnormalities in testis size, spermatogenic cycle, timing of meiotic onset, or marker gene expression of spermatogonia and spermatocytes. Taken together, these data indicate that the production of germ cell‐specificMgavariant mRNA is dispensable not only for viability but also for gametogenesis.