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m⁶依赖A的母体mRNA清除促进斑马鱼从母体转变为胚胎

Boxuan Simen Zhao^1,2, Xiao Wang^1,2, Alana V Beadell³

¹Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.

|February 14, 2017

概括

斑马鱼胚胎使用N6甲基氨酸 (m6A) 修饰来清除母体信使RNA (mRNA). 这一由Ythdf2促进的过程对于母亲及时过渡到胚胎 (MZT) 和正常发育至关重要.

科学领域:

发育生物学
表观遗传学
核糖核酸生物学

背景情况:

孕产妇到胚胎的过渡 (MZT) 调节了早期的胚胎发育,但调节因素在很大程度上仍未知.
在胚胎激活之前,母体的信使RNAs (mRNAs) 在早期胚胎发生过程中提供必要的蛋白质.

研究的目的:

研究N6甲基氨酸 (m6A) 修饰在斑马鱼MZT期间调节母体mRNA清除中的作用.
确定涉及m⁶A介导的母体mRNA衰变及其对胚胎发育的影响.

主要方法:

在斑马鱼胚胎中对母体mRNA进行量化.
在斑马鱼中使用基因敲除的m6A结合蛋白Ythdf2的功能分析.
对母体mRNA衰变率,胚胎基因组激活,细胞周期进展和发育结果的评估.

主要成果:

超过三分之一的斑马鱼母体mRNA被m6A修饰.
m6A结合蛋白Ythdf2促进了m6A修饰的母体mRNA的清除.
失去Ythdf2导致母体mRNA衰变减缓,细胞基因组激活受损,细胞循环停止和发育延迟.

结论:

m⁶依赖A的RNA衰变是一种新的,由母体调节的机制,控制斑马鱼MZT期间的母体mRNA清除.
在动物发育所需的转录组切换中,mRNA甲基化起着至关重要的作用.

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