SON controls mouse early embryonic development by regulating RNA splicing and histone methylation

in Reproduction
Authors:
Jiarui Wei J Wei, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, The First Hospital of Jilin University, Changchun, China

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Xing Lan An X An, First Hospital, Jilin University,, Jilin University, Changchun, China

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Cong Fu C Fu, First Hospital, Jilin University, Jilin University, Changchun, China

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Qi Li Q Li, First Hospital, Jilin University, Jilin University, Changchun, China

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Fang Wang F Wang, First Hospital, Jilin University, Jilin University, Changchun, China

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Rong Huang R Huang, First Hospital, Jilin University, Jilin University, Changchun, China

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Haibo Zhu H Zhu, First Hospital, Jilin University, Jilin University, Changchun, China

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Ziyi Li Z Li, First Hospital, Jilin University, Jilin University, Changchun, China

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Sheng Zhang S Zhang, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, The First Hospital of Jilin University, Chang Chun, 130062, China

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Correspondence: Sheng Zhang, Email: jluzs0520@jlu.edu.cn
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Thousands of genes are activated in late 2-cell embryos, which means that numerous pre-mRNAs are generated during this time. These pre-mRNAs must be accurately spliced to ensure that the mature mRNAs are translated to functional proteins. However, little is known about the roles of pre-mRNA splicing and cellular factors modulating pre-mRNA splicing during early embryonic development. Here, we report that downregulation of SON, a large Ser/Arg (SR)-related protein, reduced embryonic development and caused deficient blastomere cleavage. These embryonic developmental defects result from dysregulated nuclear speckle organization and pre-mRNA splicing of a set of cell cycle-related genes. Furthermore, SON downregulation disrupted the transcriptome (2128 upregulated and 1399 downregulated) in 4-cell embryos. Increased H3K4me3, H3K9me3 and H3K27me3 levels were detected in 4-cell embryos after SON downregulation. Taken together, these results demonstrate that accurate pre-mRNA splicing is essential for early embryonic development and that SON plays important roles in nuclear speckle organization, pre-mRNA splicing, transcriptome establishment and histone methylation reprogramming during early embryonic development.