Remodeling of maternal mRNA through poly(A) tail orchestrates human oocyte-to-embryo transition.
Remodeling of maternal mRNA through poly(A) tail orchestrates human oocyte-to-embryo transition.
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DOI：
10.1038/s41594-022-00908-2
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发表时间：
2023-02
影响因子：
16.8
通讯作者：
Lu F
中科院分区：
文献类型：
--
作者：
Liu Y;Zhao H;Shao F;Zhang Y;Nie H;Zhang J;Li C;Hou Z;Chen ZJ;Wang J;Zhou B;Wu K;Lu F
Poly（A）-tail介导的母体mRNA的转录后调节在卵母细胞向胚胎转变（OET）中是至关重要的。在人类OET期间，对poly（A）尾动力学一无所知。在这里，我们使用包含poly（A）的RNA亚型测序（PAIso-seq）表明，poly（A）尾长和内部非A残基在人类OET期间高度动态变化。出乎意料的是，母体mRNA经历整体重塑：在去腺苷酸化或部分降解成3个β-UTR后，它们被重新聚腺苷酸化以产生聚腺苷酸化的降解中间体，与非A残基（特别是内部长连续U残基）大量掺入新合成的聚（A）尾相一致。此外，TUT 4和TUT 7有助于这些U残基的掺入，BTG 4介导的去腺苷酸化产生母体mRNA再聚腺苷酸化的底物，并且TENT 4A和TENT 4 B掺入内部G残基。使用PAIso-seq 2进一步证实母体mRNA重塑。重要的是，母体mRNA重塑对于人类胚胎的第一次卵裂至关重要。总之，这些发现拓宽了我们对人类OET期间母体mRNA转录后调控的理解。在整个人类卵母细胞和植入前胚胎发育过程中全面的多聚腺苷酸RNA异构体测序揭示了多聚腺苷酸尾介导的母体mRNA重塑，这对人类胚胎发育至关重要。
Poly(A)-tail-mediated post-transcriptional regulation of maternal mRNAs is vital in the oocyte-to-embryo transition (OET). Nothing is known about poly(A) tail dynamics during the human OET. Here, we show that poly(A) tail length and internal non-A residues are highly dynamic during the human OET, using poly(A)-inclusive RNA isoform sequencing (PAIso-seq). Unexpectedly, maternal mRNAs undergo global remodeling: after deadenylation or partial degradation into 3ʹ-UTRs, they are re-polyadenylated to produce polyadenylated degradation intermediates, coinciding with massive incorporation of non-A residues, particularly internal long consecutive U residues, into the newly synthesized poly(A) tails. Moreover, TUT4 and TUT7 contribute to the incorporation of these U residues, BTG4-mediated deadenylation produces substrates for maternal mRNA re-polyadenylation, and TENT4A and TENT4B incorporate internal G residues. The maternal mRNA remodeling is further confirmed using PAIso-seq2. Importantly, maternal mRNA remodeling is essential for the first cleavage of human embryos. Together, these findings broaden our understanding of the post-transcriptional regulation of maternal mRNAs during the human OET. Comprehensive poly(A)-inclusive RNA isoform sequencing throughout the human oocyte and preimplantation embryo development reveals poly(A)-tail-mediated maternal mRNA remodeling that is essential for human embryo development.
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