The RNA-binding protein Seb4/RBM24 is a direct target of MyoD and is required for myogenesis during Xenopus early development

The RNA-binding protein Seb4/RBM24 is a direct target of MyoD and is required for myogenesis during Xenopus early development
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RNA 结合蛋白 Seb4/RBM24 是 MyoD 的直接靶标,是非洲爪蟾早期发育过程中肌生成所必需的

DOI:
10.1016/j.mod.2010.03.002
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发表时间:
2010-05-01
影响因子:
2.6
通讯作者:
Shi, De-Li
Shi, De-Li
中科院分区:
生物学4区
文献类型:
--
作者:
Li, Hong-Yan;Bourdelas, Audrey;Shi, De-Li

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在早期发育过程中,RNA结合蛋白在转录后调控基因表达中起着重要作用,它们表现出时空调控的表达模式。非洲爪哇Seb4基因,在其他脊椎动物中也被称为RBM24,在原肠发育过程中被限制在侧面和腹侧中胚层,然后定位到体细胞中胚层,与XMyoD基因类似,使用激素诱导形式的MyoD来识别潜在的直接MyoD靶基因,我们发现Seb4的表达在原肠胚期受到MyoD的直接调控。我们进一步证明,一个0.65kb的X tropicalsRBM24调节区包含多个E盒(CANNTG),通过在X LAMS胚胎的动物极点注射RBM24报告基因,我们发现该报告基因确实被MyoD特异性激活,并被显性负MyoD突变体抑制。敲除Seb4产生与显性负MyoD突变体相似的效果,表明在培养的外胚层外植体中,它是成肌基因表达和肌肉发生所必需的,尽管过表达Seb4对肌肉发生没有明显的影响。抑制Seb4基因的表达可抑制MyoD诱导的成肌基因表达这些结果表明,Seb4是MyoD在成肌过程中的靶标,是成肌基因表达所必需的(C)2010爱思唯尔爱尔兰有限公司版权所有
RNA-binding proteins play an important role to post-transcnptionally regulate gene expression During early development they exhibit temporally and spatially regulated expression pattern The expression of Xenopus loans Seb4 gene, also known as RBM24 in other vertebrates, is restricted to the lateral and ventral mesoderm during gastrulation and then localized to the somitic mesoderm, in a similar pattern as XMyoD gene Using a hormone-inducible form of MyoD to identify potential direct MyoD target genes, we find that Seb4 expression is directly regulated by MyoD at the gastrula stage We further show that a 0 65 kb X tropicalis RBM24 regulatory region contains multiple E boxes (CANNTG), which are potential binding sites for MyoD and other bHLH proteins By injecting a RBM24 reporter construct into the animal pole of X lams embryos, we find that this reporter gene is indeed specifically activated by MyoD and repressed by a dominant negative MyoD mutant Knockdown of Seb4 produces similar effects as those obtained by the dominant negative MyoD mutant, indicating that it is required for the expression of myogenic genes and myogenesis in the embryo In cultured ectodermal explants, although overexpression of Seb4 has no obvious effect on myogenesis, knockdown of Seb4 inhibits the expression of myogenic genes and myogenesis induced by MyoD These results reveal that Seb4 is a target of MyoD during myogenesis and is required for myogenic gene expression (C) 2010 Elsevier Ireland Ltd All rights reserved