miR-129-3p controls cilia assembly by regulating CP110 and actin dynamics.
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.
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.
Jingli
J
Cao
Yidong
Y
Shen
Lei
L
Zhu
Yanan
Y
Xu
Yizhuo
Y
Zhou
Zhili
Z
Wu
Yiping
Y
Li
Xiumin
X
Yan
Xueliang
X
Zhu
D020413:3' Untranslated Regions; D008841:Actin Cytoskeleton / Q000378:metabolism*; D051377:Actin-Related Protein 2 / Q000235:genetics / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D002502:Centrioles / Q000378:metabolism*; D002923:Cilia / Q000378:metabolism; D017124:Conserved Sequence; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D017930:Genes, Reporter; D057809:HEK293 Cells; D006801:Humans; D060588:LIM Domain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009024:Morphogenesis; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D060910:Pronephros / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D055213:Retinal Pigment Epithelium / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D015027:Zebrafish / Q000196:embryology / Q000235:genetics
D020413:3' Untranslated Regions; C107440:ABLIM1 protein, human; C495926:ACTR2 protein, human; D051377:Actin-Related Protein 2; D000199:Actins; C467559:CCP110 protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C482527:FNBP1L protein, human; D060588:LIM Domain Proteins; D035683:MicroRNAs; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; C541915:Mirn129 microRNA, human; D010750:Phosphoproteins