NSUN7是一种催化不活的RNAm5C甲基转移酶,对于精子鞭毛组装至关重要
Jing Li1, Wen-Yu Zhu1, Zhen Wang1
1School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
Nature communications
|December 11, 2025
概括
作为RNA修饰酶家族成员的NSUN7,由于SAM结合的改变,它不能催化RNA5-甲基细胞素 (m5C). 它在精子运动和组织方面发挥着非催化作用.
科学领域:
- 表观遗传学和分子生物学
- 基因组RNA的修改 基因组RNA的改变
- 精子发生和男性生育能力.
背景情况:
- RNA5-甲基细胞酶 (m5C) 是一个关键的表达体记号,主要由NSUN家族的甲基转移酶调节.
- 尽管已确定NSUN7与男性不孕症的联系,但NSUN7的酶活性和特定的生物功能仍然基本上没有被描述.
研究的目的:
- 研究NSUN7在RNA m5C修饰和精子生成中的催化活性和生理作用.
- 在NSUN家族的背景下,阐明NSUN7的功能背后的分子机制.
主要方法:
- 在Nsun7淘汰赛小鼠中进行了全转录组m5C质谱和超快速二硫酸盐测序.
- 对NSUN7蛋白序列进行分析,以寻找参与S-adenosylmethionine (SAM) 结合的保存基因.
- 单细胞RNA测序以评估Nsun7缺乏精子体中的mRNA表达变化.
- 评估精子运动性和精子结构 (轴突,纵向柱).
主要成果:
- 在成年老鼠丸中,NSUN7的表达很高,特别是在长长的精子体中.
- Nsun7淘汰赛没有影响全球RNA m5C水平,表明缺乏催化活性.
- 由于基因IV中的关键氨基酸替代,NSUN7缺乏SAM结合能力,这证实了其非酶性质.
- 缺少NSUN7导致精子的渐进性运动性受损,精子轴突的结构缺陷,以及纵向柱的错位.
- 单细胞RNA测序揭示了Nsun7淘汰精子体中状组织相关的mRNAs的减少表达.
结论:
- NSUN7是NSUN家族的非催化成员,缺乏甲基化RNA的能力.
- NSUN7在调节精子运动和精子结构方面发挥着至关重要的非酶作用,通过影响参与组织的基因表达来调节精子运动和精子结构.
- 这些发现澄清了NSUN7的功能,并扩大了对NSUN家族内的多样性角色的理解.
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