Blastocyst formation represents the first lineage specification by segregation of the trophectoderm from the inner cell mass in early embryonic development. Transcriptional regulation of Cdx2, which is selectively expressed in and essential for the specification of trophectoderm, has been extensively studied. However, post-transcriptional regulation of Cdx2 remains largely unknown. In this study, we report that RNA-binding protein motif 46 (Rbm46), an RNA-binding motif protein with unknown function, directly binds to and stabilizes Cdx2 mRNA in early mouse embryos. In addition, knockdown of Rbm46 using RNA interference downregulated the majority of trophectoderm markers in mouse embryonic stem cells and blocked the allocation of blastomere cells to the trophectoderm in mouse embryos. Our study revealed a novel mechanism by which Rbm46 regulates trophectoderm specification through stabilizing Cdx2 mRNA in early mouse embryos.
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