Rbms3 functions in craniofacial development by posttranscriptionally modulating TGF-β signaling.
Rbms3 functions in craniofacial development by posttranscriptionally modulating TGF-β signaling.
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DOI：
10.1083/jcb.201204138
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发表时间：
2012-10-29
期刊：
影响因子：
--
通讯作者：
Bronner ME
中科院分区：
文献类型：
--
作者：
Jayasena CS;Bronner ME
Rbms 3通过结合和稳定Smad 2转录物来调节TGF-βr信号传导，这是软骨形成的关键途径。颅神经嵴细胞形成了面部骨骼的大部分，它们发育的异常会导致严重的出生缺陷。在一个新的斑马鱼蛋白陷阱屏幕，我们确定了RNA结合蛋白，Rbms 3，这是瞬时表达的细胞质中凝聚的神经嵴细胞内的咽弓。rbms 3的变形体显示软骨形成前嵴的增殖减少，软骨形成/成骨谱系标记物的表达显著改变。这种表型与在TGF-βr2：Wnt 1-Cre突变体中观察到的软骨/嵴缺陷非常相似，这表明可能与TGF-β信号传导有关。与此相一致的发现是：（a）Rbms 3稳定了具有smad 2 3′非翻译区的报告转录本，（B）全长Rbms 3的RNA免疫沉淀显示了smad 2/3的富集，以及（c）rbms 3变体中pSmad 2水平降低。总之，这些结果表明，Rbms 3转录后调节促进软骨形成的主要途径之一，转化生长因子β受体（TGF-βr）途径。
Rbms3 regulates TGF-βr signaling, a critical pathway for chondrogenesis, by binding and stabilizing Smad2 transcripts. Cranial neural crest cells form much of the facial skeleton, and abnormalities in their development lead to severe birth defects. In a novel zebrafish protein trap screen, we identified an RNA-binding protein, Rbms3, that is transiently expressed in the cytoplasm of condensing neural crest cells within the pharyngeal arches. Morphants for rbms3 displayed reduced proliferation of prechondrogenic crest and significantly altered expression for chondrogenic/osteogenic lineage markers. This phenotype strongly resembles cartilage/crest defects observed in Tgf-βr2:Wnt1-Cre mutants, which suggests a possible link with TGF-β signaling. Consistent with this are the findings that: (a) Rbms3 stabilized a reporter transcript with smad2 3′ untranslated region, (b) RNA immunoprecipitation with full-length Rbms3 showed enrichment for smad2/3, and (c) pSmad2 levels were reduced in rbms3 morphants. Overall, these results suggest that Rbms3 posttranscriptionally regulates one of the major pathways that promotes chondrogenesis, the transforming growth factor β receptor (TGF-βr) pathway.
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影响因子：
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作者：
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DOI：
10.1073/pnas.0603730103
发表时间：
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