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N-甲基腺苷调节卵母细胞中的母体RNA维持以及小鼠母源-合子转变期间的RNA及时降解。

N-methyladenosine regulates maternal RNA maintenance in oocytes and timely RNA decay during mouse maternal-to-zygotic transition.

作者信息

Wu You, Xu Xiaocui, Qi Meijie, Chen Chuan, Li Mengying, Yan Rushuang, Kou Xiaochen, Zhao Yanhong, Liu Wenqiang, Li Yanhe, Liu Xuelian, Zhang Meiling, Yi Chengqi, Liu Hongbin, Xiang Junhong, Wang Hong, Shen Bin, Gao Yawei, Gao Shaorong

机构信息

Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.

Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, China.

出版信息

Nat Cell Biol. 2022 Jun;24(6):917-927. doi: 10.1038/s41556-022-00915-x. Epub 2022 May 23.

Abstract

N-methyladenosine (mA) and its regulatory components play critical roles in various developmental processes in mammals. However, the landscape and function of mA in early embryos remain unclear owing to limited materials. Here we developed a method of ultralow-input mA RNA immunoprecipitation followed by sequencing to reveal the transcriptome-wide mA landscape in mouse oocytes and early embryos and found unique enrichment and dynamics of mA RNA modifications on maternal and zygotic RNAs, including the transcripts of transposable elements MTA and MERVL. Notably, we found that the maternal protein KIAA1429, a component of the mA methyltransferase complex, was essential for mA deposition on maternal mRNAs that undergo decay after zygotic genome activation and MTA transcripts to maintain their stability in oocytes. Interestingly, mA methyltransferases, especially METTL3, deposited mA on mRNAs transcribed during zygotic genome activation and ensured their decay after the two-cell stage, including Zscan4 and MERVL. Together, our findings uncover the essential functions of mA in specific contexts during the maternal-to-zygotic transition, namely ensuring the stability of mRNAs in oocytes and the decay of two-cell-specific transcripts after fertilization.

摘要

N-甲基腺苷(mA)及其调控成分在哺乳动物的各种发育过程中发挥着关键作用。然而,由于材料有限,早期胚胎中mA的全貌和功能仍不清楚。在这里,我们开发了一种超低输入量的mA RNA免疫沉淀测序方法,以揭示小鼠卵母细胞和早期胚胎中转录组范围内的mA全貌,并发现母源RNA和合子RNA上mA RNA修饰的独特富集和动态变化,包括转座元件MTA和MERVL的转录本。值得注意的是,我们发现母源蛋白KIAA1429是mA甲基转移酶复合物的一个组成部分,对于合子基因组激活后发生降解的母源mRNA上的mA沉积以及MTA转录本在卵母细胞中维持其稳定性至关重要。有趣的是,mA甲基转移酶,尤其是METTL3,在合子基因组激活期间转录的mRNA上沉积mA,并确保它们在二细胞阶段后降解,包括Zscan4和MERVL。总之,我们的研究结果揭示了mA在母源-合子转变的特定背景下的重要功能,即确保卵母细胞中mRNA的稳定性以及受精后二细胞特异性转录本的降解。

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