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XB-ART-49113
Nature June 5, 2014; 510 (7503): 115-20.

miR-34/449 miRNAs are required for motile ciliogenesis by repressing cp110.

Song R , Walentek P , Sponer N , Klimke A , Lee JS , Dixon G , Harland R , Wan Y , Lishko P , Lize M , Kessel M , He L .


Abstract
The mir-34/449 family consists of six homologous miRNAs at three genomic loci. Redundancy of miR-34/449 miRNAs and their dominant expression in multiciliated epithelia suggest a functional significance in ciliogenesis. Here we report that mice deficient for all miR-34/449 miRNAs exhibited postnatal mortality, infertility and strong respiratory dysfunction caused by defective mucociliary clearance. In both mouse and Xenopus, miR-34/449-deficient multiciliated cells (MCCs) exhibited a significant decrease in cilia length and number, due to defective basal body maturation and apical docking. The effect of miR-34/449 on ciliogenesis was mediated, at least in part, by post-transcriptional repression of Cp110, a centriolar protein suppressing cilia assembly. Consistent with this, cp110 knockdown in miR-34/449-deficient MCCs restored ciliogenesis by rescuing basal body maturation and docking. Altogether, our findings elucidate conserved cellular and molecular mechanisms through which miR-34/449 regulate motile ciliogenesis.

PubMed ID: 24899310
PMC ID: PMC4119886
Article link: Nature
Grant support: [+]
Genes referenced: actl6a ccp110 ctrl foxj1 foxj1.2 gnl3 kidins220 mcc tub tuba4b
GO keywords: regulation of cilium assembly

Disease Ontology terms: lung disease

Article Images: [+] show captions
References:
Ambros, 2004, Pubmed [+]


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