Eukaryotic initiation factor 4A3 inhibits Wnt/β-catenin signaling and regulates axis formation in zebrafish embryos.
Eukaryotic initiation factor 4A3 inhibits Wnt/β-catenin signaling and regulates axis formation in zebrafish embryos.
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DOI：
10.1242/dev.198101
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发表时间：
2021-05
期刊：
影响因子：
4.6
通讯作者：
Bo Wang;Xiaozhi Rong;Yumei Zhou;Yunzhang Liu;Jiqin Sun;Beibei Zhao;Bei Deng;Lei Lu;Ling Lu-Lin
中科院分区：
文献类型：
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作者：
Bo Wang;Xiaozhi Rong;Yumei Zhou;Yunzhang Liu;Jiqin Sun;Beibei Zhao;Bei Deng;Lei Lu;Ling Lu-Lin
经典Wnt信号传导激活的关键步骤是β-catenin和Tcf/Lefs之间的相互作用，其形成转录激活复合物并促进靶基因的表达。真核起始因子4A 3（EIF 4A 3）是一种ATP依赖的DEAD盒家族RNA解旋酶，是外显子连接复合物（EJC）的核心亚基，控制一系列RNA转录后过程。在本研究中，我们发现EIF 4A 3作为Wnt抑制剂通过干扰β-catenin/Tcf转录激活复合物的形成而发挥作用。随着Wnt刺激的增加，积累的β-连环蛋白从具有Tcf/Lef的转录复合物中置换EIF 4A 3，使活性复合物促进靶基因的表达。在斑马鱼胚胎中，eif 4a 3缺失通过增加Wnt/β-catenin信号传导抑制背侧组织者的发育和前神经外胚层的图案形成。相反，eif 4a 3的过表达降低了Wnt/β-catenin信号传导，并抑制了原肠胚形成前背侧组织者的形成。我们的研究结果揭示了EIF 4A 3在抑制Wnt信号和调节斑马鱼胚胎发育中的作用。
A key step in the activation of canonical Wnt signaling is the interaction between β-catenin and Tcf/Lefs that forms the transcription activation complex and facilitates the expression of target genes. Eukaryotic initiation factor 4A3 (EIF4A3) is an ATP-dependent DEAD box-family RNA helicase and acts as a core subunit of the exon junction complex (EJC) to control a series of RNA post-transcriptional processes. In this study, we uncover that EIF4A3 functions as a Wnt inhibitor by interfering with the formation of β-catenin/Tcf transcription activation complex. As Wnt stimulation increases, accumulated β-catenin displaces EIF4A3 from a transcriptional complex with Tcf/Lef, allowing the active complex to facilitate the expression of target genes. In zebrafish embryos, eif4a3 depletion inhibited the development of the dorsal organizer and pattern formation of the anterior neuroectoderm by increasing Wnt/β-catenin signaling. Conversely, overexpression of eif4a3 decreased Wnt/β-catenin signaling and inhibited the formation of the dorsal organizer before gastrulation. Our results reveal previously unreported roles of EIF4A3 in the inhibition of Wnt signaling and the regulation of embryonic development in zebrafish.