miR-34/449 miRNAs are required for motile ciliogenesis by repressing cp110
| Autor: | Joon Sub Lee, Rui Song, Polina V. Lishko, Lin He, Richard M. Harland, Muriel Lizé, Ying Wan, Michael Kessel, Alexander Klimke, Peter Walentek, Nicole Sponer, Gary Dixon |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Centriole Respiratory System Xenopus Mice Xenopus laevis 0302 clinical medicine Morphogenesis 2.1 Biological and endogenous factors Basal body Aetiology Lung Centrioles Mice Knockout Pediatric Genetics 0303 health sciences Gene knockdown Multidisciplinary biology Cilium Cell biology Phenotype 030220 oncology & carcinogenesis Female Biotechnology General Science & Technology Knockout Article 03 medical and health sciences Ciliogenesis microRNA Animals Cilia 030304 developmental biology Base Sequence Kartagener Syndrome Contraception/Reproduction Newborn biology.organism_classification Survival Analysis Basal Bodies MicroRNAs Animals Newborn Infertility Calmodulin-Binding Proteins Generic health relevance Epidermis |
| Zdroj: | Nature, vol 510, iss 7503 Nature |
| ISSN: | 1476-4687 0028-0836 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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