Mechanism of embryonic arrest caused by maternal mRNA decay failure and R-loop accumulation (IMAGE)
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A mechanism by which knockouts of maternal mRNA clearing factors lead to zygotic arrest in mice. Abnormal accumulation of maternal mRNAs in mouse zygotes leads to transcriptional leakage before the correct timing of ZGA, which is the primary cause of excessive R-loop formation and genome instability. Maternal mRNA excess-associated increases in chromatin accessibility leads to precocious transcription and R-loop formation in zygotes after pronuclear formation. Accumulated R-loops in the pronuclei impair zygotic DNA replication, increase genomic instability, and cause S-phase arrest of the first zygotic cell cycle.
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