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

Thousands of genes are activated at later 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 resulted from dysregulated nuclear speckle organization and pre-mRNA splicing of a set of cell-cycle-related genes. Furthermore, SON downregulation disturbed the transcriptome (2128 upregulation and 1399 downregulation) in 4-cell embryos. Increased H3K4me3, H3K9me3 and H3K27me3 levels were found in 4-cell embryos after SON downregulation. Taken together, those results demonstrate that accurate pre-mRNA splicing is essential for early embryonic development, and SON plays important roles on nuclear speckle organization, pre-mRNA splicing, the transcriptome establishment and histone methylation reprogramming during early embryonic development. In order to study the roles of SON on mice early embryonic development, we microinjeted siRNA of SON into zygotes to knockdown SON lelvel.