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PABPN1L mediates cytoplasmic mRNA decay as a placeholder during the maternal-to-zygotic transition.
EMBO Reports ( IF 6.5 ) Pub Date : 2020-06-17 , DOI: 10.15252/embr.201949956
Long-Wen Zhao 1 , Ye-Zhang Zhu 1 , Hao Chen 1 , Yun-Wen Wu 1 , Shuai-Bo Pi 1 , Lu Chen 1 , Li Shen 1 , Heng-Yu Fan 1, 2
Affiliation  

Maternal mRNA degradation is a critical event of the maternal‐to‐zygotic transition (MZT) that determines the developmental potential of early embryos. Nuclear Poly(A)‐binding proteins (PABPNs) are extensively involved in mRNA post‐transcriptional regulation, but their function in the MZT has not been investigated. In this study, we find that the maternally expressed PABPN1‐like (PABPN1L), rather than its ubiquitously expressed homolog PABPN1, acts as an mRNA‐binding adapter of the mammalian MZT licensing factor BTG4, which mediates maternal mRNA clearance. Female Pabpn1l null mice produce morphologically normal oocytes but are infertile owing to early developmental arrest of the resultant embryos at the 1‐ to 2‐cell stage. Deletion of Pabpn1l impairs the deadenylation and degradation of a subset of BTG4‐targeted maternal mRNAs during the MZT. In addition to recruiting BTG4 to the mRNA 3ʹ‐poly(A) tails, PABPN1L is also required for BTG4 protein accumulation in maturing oocytes by protecting BTG4 from SCF‐βTrCP1 E3 ubiquitin ligase‐mediated polyubiquitination and degradation. This study highlights a noncanonical cytoplasmic function of nuclear poly(A)‐binding protein in mRNA turnover, as well as its physiological importance during the MZT.

中文翻译:

PABPN1L 在母体向合子过渡期间介导细胞质 mRNA 衰变作为占位符。

母体 mRNA 降解是母体向合子转变 (MZT) 的关键事件,它决定了早期胚胎的发育潜力。核聚 (A) 结合蛋白 (PABPNs) 广泛参与 mRNA 转录后调控,但尚未研究其在 MZT 中的功能。在这项研究中,我们发现母体表达的 PABPN1 样 (PABPN1L),而不是其普遍表达的同源物 PABPN1,充当哺乳动物 MZT 许可因子 BTG4 的 mRNA 结合接头,其介导母体 mRNA 清除。雌性Pabpn1l缺失小鼠产生形态正常的卵母细胞,但由于所得胚胎在 1 至 2 细胞阶段的早期发育停滞而无法生育。删除Pabpn1l在 MZT 期间损害 BTG4 靶向母体 mRNA 子集的去腺苷酸化和降解。除了将 BTG4 募集到 mRNA 3′-poly(A) 尾部外,PABPN1L 也是成熟卵母细胞中 BTG4 蛋白积累所必需的,它保护 BTG4 免受 SCF-βTrCP1 E3 泛素连接酶介导的多泛素化和降解。这项研究强调了核聚 (A) 结合蛋白在 mRNA 转换中的非典型细胞质功能,以及它在 MZT 期间的生理重要性。
更新日期:2020-08-05
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