State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China.
Nat Cell Biol. 2012 Jun 10;14(7):697-706. doi: 10.1038/ncb2512.
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.
纤毛发生需要从母中心粒上除去 CP110；肌动蛋白动力学也会影响纤毛发生，至少部分是通过影响纤毛发生的膜小泡向中心粒的积累。这些不同的过程是如何被正确调节的仍然未知。在这里，我们表明，miR-129-3p，一种在脊椎动物中保守的 microRNA，通过同时下调 CP110 和抑制分支的 F-肌动蛋白形成，来控制培养细胞中的纤毛发生。阻断 miR-129-3p 抑制了血清饥饿诱导的纤毛发生，而其过表达则在增殖细胞中强烈诱导纤毛发生，并促进纤毛伸长。基因表达分析进一步确定了 ARP2、TOCA1、ABLIM1 和 ABLIM3 是其在纤毛发生相关的肌动蛋白动力学中的靶基因。此外，斑马鱼胚胎中 miR-129-3p 的抑制抑制了 Kupffer 囊泡和前肾的纤毛发生，并诱导了发育异常，包括弯曲的身体、心包水肿和左右不对称缺陷。因此，我们的结果揭示了一种通过 microRNA 介导的转录后调控来协调中心粒-基底体过渡和随后的纤毛组装的机制。
