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
-
- Binding Sites
- Cilia/metabolism
- RNA Processing, Post-Transcriptional
- Molecular Sequence Data
- Transfection
- HEK293 Cells
- Humans
- Actin-Related Protein 2/genetics
- Actin-Related Protein 2/metabolism
- Pronephros/metabolism
- Conserved Sequence
- Zebrafish/embryology
- Zebrafish/genetics
- Animals
- 3' Untranslated Regions
- Mice
- Microfilament Proteins/genetics
- Microfilament Proteins/metabolism
- Actin Cytoskeleton/metabolism*
- Morphogenesis
- Gene Expression Regulation, Developmental
- Time Factors
- Phosphoproteins/genetics
- Phosphoproteins/metabolism*
- LIM Domain Proteins/genetics
- LIM Domain Proteins/metabolism
- MicroRNAs/metabolism*
- Microtubule-Associated Proteins/genetics
- Microtubule-Associated Proteins/metabolism*
- Genes, Reporter
- Retinal Pigment Epithelium/metabolism*
- Cell Proliferation
- Centrioles/metabolism*
- Gene Knockdown Techniques
- Carrier Proteins/genetics
- Carrier Proteins/metabolism
- Signal Transduction
- Actins/metabolism*
- Base Sequence
- Cell Cycle Proteins/genetics
- Cell Cycle Proteins/metabolism*
- 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.