miR-129-3p controls cilia assembly by regulating CP110 and actin dynamics
- Authors
- Cao, J., Shen, Y., Zhu, L., Xu, Y., Zhou, Y., Wu, Z., Li, Y., Yan, X., and Zhu, X.
- ID
- ZDB-PUB-120612-8
- Date
- 2012
- Source
- Nature cell biology 14(7): 697-706 (Journal)
- Registered Authors
- Cao, Jingli
- Keywords
- none
- MeSH Terms
-
- Zebrafish/embryology
- Zebrafish/genetics
- HEK293 Cells
- Microtubule-Associated Proteins/genetics
- Microtubule-Associated Proteins/metabolism*
- Centrioles/metabolism*
- Microfilament Proteins/genetics
- Microfilament Proteins/metabolism
- Conserved Sequence
- Mice
- Gene Knockdown Techniques
- LIM Domain Proteins/genetics
- LIM Domain Proteins/metabolism
- Signal Transduction
- Molecular Sequence Data
- Phosphoproteins/genetics
- Phosphoproteins/metabolism*
- Time Factors
- Gene Expression Regulation, Developmental
- Genes, Reporter
- Binding Sites
- Retinal Pigment Epithelium/metabolism*
- Cell Cycle Proteins/genetics
- Cell Cycle Proteins/metabolism*
- Humans
- Transfection
- Base Sequence
- Pronephros/metabolism
- Carrier Proteins/genetics
- Carrier Proteins/metabolism
- Cell Proliferation
- Morphogenesis
- Cilia/metabolism
- Animals
- Actin Cytoskeleton/metabolism*
- MicroRNAs/metabolism*
- Actin-Related Protein 2/genetics
- Actin-Related Protein 2/metabolism
- 3' Untranslated Regions
- Actins/metabolism*
- RNA Processing, Post-Transcriptional
- PubMed
- 22684256 Full text @ Nat. Cell Biol.
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.