期刊
NUCLEIC ACIDS RESEARCH
卷 50, 期 1, 页码 458-472出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkab1213
关键词
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资金
- National Natural Science Foundation of China [31930031, 31890781]
- National Ten-Thousands Talents Program of China
- Natural Science Foundation of Zhejiang Province, China [D22C68649]
- Key Research and Development Program of Zhejiang Province [2021C03098, 2021C03100]
This study identified the nuclear poly(A) binding protein 1 (PABPN1) as a crucial factor for maternal mRNA decay and revealed its cytoplasmic function in early embryonic development. Depletion of PABPN1 in mice resulted in developmental arrest and mortality at the preimplantation stage, with a failure to remove maternal mRNAs via the Z-decay pathway. PABPN1-mediated Z-decay plays a key role in major zygotic genome activation and regulates the expression of cell fate-determining factors in mouse preimplantation embryos.
An embryo starts its life with maternal mRNA clearance, which is crucial for embryonic development. The elimination of maternal transcripts occurs by the joint action of two pathways: the maternally encoded mRNA decay pathway (M-decay) and the zygo tic genome activation (ZGA)-dependent pathway (Z-decay). However, zygotic factors triggering maternal mRNA decay in early mammalian embryos remain largely unknown. In this study, we identified the zygotically encoded nuclear poly(A) binding protein 1 (PABPN1) as a factor required for maternal mRNA turnover, with a previously undescribed cytoplasmic function. Cytoplasmic PABPN1 docks on 3'-uridylated transcripts, downstream of terminal uridylyl transferases TUT4 and TUT7, and recruits 3'-5' exoribonuclease DIS3L2 to its targets, facilitating maternal mRNA decay. Pabpnl-knockout in mice resulted in preimplantation stage mortality due to early developmental arrest at the morula stage. Maternal mRNAs to be eliminated via the Z-decay pathway failed to be removed from Pabpn1-depleted embryos. Furthermore, PABPN1-mediated Z-decay is essential for major ZGA and regulates the expression of cell fate-determining factors in mouse preimplantation embryos. This study revealed an unforeseen cytoplasmic function of PABPN1 coupled with early embryonic development, characterized the presence of a zygotic destabilizer of maternal mRNA, and elucidated the Z-decay process mechanisms, which potentially contribute to human fertility.
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