Maternal mRNA deadenylation and allocation via Rbm14 condensates facilitate vertebrate blastula development
Maternal mRNA deadenylation and allocation via Rbm14 condensates facilitate vertebrate blastula development
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DOI：
10.15252/embj.2022111364
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发表时间：
2022-12
期刊：
影响因子：
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通讯作者：
Yue Xiao;Jiehui Chen;Suming Yang;Honghua Sun;Lele Xie;Jinsong Li;N. Jing;Xueliang Zhu
中科院分区：
文献类型：
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作者：
Yue Xiao;Jiehui Chen;Suming Yang;Honghua Sun;Lele Xie;Jinsong Li;N. Jing;Xueliang Zhu
早期胚胎发育取决于母体转录组的适当利用和清除。这些过程是如何在时空上调节的仍然不清楚。在这里，我们发现核RNA结合蛋白Rbm14和母体mRNA共相分离成细胞质浓缩物，以促进脊椎动物囊胚到原肠胚的发育。在斑马鱼中，Rbm14凝聚物是非常丰富的卵裂球和显着减少后显着激活合子转录。它们通过与中心体γ微管蛋白点结合而集中在纺锤体极，并且在8细胞和16细胞胚胎中主要表现出不对称分裂，在胚胎中线上具有整体对称性。它们的形成受到m6A的剂量依赖性刺激，但受到母体mRNA的m5C修饰的抑制。此外，去腺苷酶Parn与这些缩合物共相分离，这是早期卵裂球中mRNA去腺苷化所必需的。Rbm14的耗竭损害了斑马鱼和小鼠的胚胎细胞分化和合子基因组的完全激活，并导致囊胚期的发育停滞。我们的研究结果表明，细胞质Rbm14冷凝物的形成通过促进m6A修饰的母体mRNA的去腺苷酸化、保护和有丝分裂分配，以及通过在受调节的拆卸后释放少聚腺苷酸转录物以允许其重新聚腺苷酸化和翻译或清除来调节早期胚胎发生。
Early embryonic development depends on proper utilization and clearance of maternal transcriptomes. How these processes are spatiotemporally regulated remains unclear. Here we show that nuclear RNA‐binding protein Rbm14 and maternal mRNAs co‐phase separate into cytoplasmic condensates to facilitate vertebrate blastula‐to‐gastrula development. In zebrafish, Rbm14 condensates were highly abundant in blastomeres and markedly reduced after prominent activation of zygotic transcription. They concentrated at spindle poles by associating with centrosomal γ‐tubulin puncta and displayed mainly asymmetric divisions with a global symmetry across embryonic midline in 8‐ and 16‐cell embryos. Their formation was dose‐dependently stimulated by m6A, but repressed by m5C modification of the maternal mRNA. Furthermore, deadenylase Parn co‐phase separated with these condensates, and this was required for deadenylation of the mRNAs in early blastomeres. Depletion of Rbm14 impaired embryonic cell differentiations and full activations of the zygotic genome in both zebrafish and mouse and resulted in developmental arrest at the blastula stage. Our results suggest that cytoplasmic Rbm14 condensate formation regulates early embryogenesis by facilitating deadenylation, protection, and mitotic allocation of m6A‐modified maternal mRNAs, and by releasing the poly(A)‐less transcripts upon regulated disassembly to allow their re‐polyadenylation and translation or clearance.