miR-129-3p controls cilia assembly by regulating CP110 and actin dynamics
miR-129-3p controls cilia assembly by regulating CP110 and actin dynamics
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miR-129-3p 通过调节 CP110 和肌动蛋白动力学来控制纤毛组装
DOI：
10.1038/ncb2512
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发表时间：
2012-07-01
影响因子：
21.3
通讯作者：
Zhu, Xueliang
中科院分区：
文献类型：
--
作者：
Cao, Jingli;Shen, Yidong;Zhu, Xueliang
纤毛发生需要从母亲中心粒中去除CP 110;肌动蛋白动力学也影响纤毛形成，至少部分是通过影响纤毛发生膜囊泡的中心体积累。如何正确监管这些不同的过程仍然未知。在这里，我们表明，miR-129- 3 p，一种在脊椎动物中保守的microRNA，通过同时下调CP 110和抑制分支的F-肌动蛋白形成来控制培养细胞中的纤毛生物发生。阻断miR-129- 3 p可抑制血清饥饿诱导的纤毛发生，而其过表达可有效诱导增殖细胞中的纤毛形成，并促进纤毛伸长。基因表达分析进一步确定ARP 2，TOCA 1，ABLIM 1和ABLIM 3作为其在纤毛相关的肌动蛋白动力学的目标。此外，在斑马鱼胚胎中抑制miR-129- 3 p抑制枯否氏囊泡和原肾中的纤毛形成，并诱导发育异常，包括弯曲的身体、心包水肿和缺陷的左右不对称。因此，我们的研究结果揭示了一种机制，通过microRNA介导的转录后调控协调中心粒到基体的过渡和随后的纤毛组装。
Ciliogenesis requires the removal of CP110 from the mother centriole; actin dynamics also influence ciliation, at least partly by affecting the centrosomal accumulation of ciliogenic membrane vesicles. How these distinct processes are properly regulated remains unknown. Here we show that miR-129-3p, a microRNA conserved in vertebrates, controlled cilia biogenesis in cultured cells by concomitantly downregulating CP110 and repressing branched F-actin formation. Blocking miR-129-3p inhibited serum-starvation-induced ciliogenesis, whereas its overexpression potently induced ciliation in proliferating cells and also promoted cilia elongation. Gene expression analysis further identified ARP2, TOCA1, ABLIM1 and ABLIM3 as its targets in ciliation-related actin dynamics. Moreover, miR-129-3p inhibition in zebrafish embryos suppressed ciliation in Kupffer’s vesicle and the pronephros, and induced developmental abnormalities including a curved body, pericardial oedema and defective left–right asymmetry. Therefore, our results reveal a mechanism that orchestrates both the centriole-to-basal body transition and subsequent cilia assembly through microRNA-mediated post-transcriptional regulation.