title: miR-34/449 miRNAs are required for motile ciliogenesis by repressing cp110.
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.
authors.affiliation: 1] Division of Cellular and Developmental Biology, MCB Department, University of California at Berkeley, Berkeley, California 94705, USA [2].
authors.forename: Rui
authors.initials: R
authors.lastname: Song
authors.affiliation: 1] Division of Genetics, Genomics and Development, Centre for Integrative Genomics, MCB Department, University of California at Berkeley, Berkeley, California 94705, USA [2].
authors.forename: Peter
authors.initials: P
authors.lastname: Walentek
authors.affiliation: 1] Division of Cellular and Developmental Biology, MCB Department, University of California at Berkeley, Berkeley, California 94705, USA [2].
authors.forename: Nicole
authors.initials: N
authors.lastname: Sponer
authors.affiliation: Department of Molecular Cell Biology, Max Planck Institute for Biophysical Chemistry, Goettingen 37077, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Klimke
authors.affiliation: Division of Cellular and Developmental Biology, MCB Department, University of California at Berkeley, Berkeley, California 94705, USA.
authors.forename: Joon Sub
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Division of Cellular and Developmental Biology, MCB Department, University of California at Berkeley, Berkeley, California 94705, USA.
authors.forename: Gary
authors.initials: G
authors.lastname: Dixon
authors.affiliation: Division of Genetics, Genomics and Development, Centre for Integrative Genomics, MCB Department, University of California at Berkeley, Berkeley, California 94705, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Harland
authors.affiliation: The Third Military Medical University, Chongqing 400038, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wan
authors.affiliation: Division of Cellular and Developmental Biology, MCB Department, University of California at Berkeley, Berkeley, California 94705, USA.
authors.forename: Polina
authors.initials: P
authors.lastname: Lishko
authors.affiliation: Department of Molecular Oncology, University of Goettingen, Goettingen 37073, Germany.
authors.forename: Muriel
authors.initials: M
authors.lastname: Lize
authors.affiliation: Department of Molecular Cell Biology, Max Planck Institute for Biophysical Chemistry, Goettingen 37077, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Kessel
authors.affiliation: Division of Cellular and Developmental Biology, MCB Department, University of California at Berkeley, Berkeley, California 94705, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: He
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D064652:Basal Bodies / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D001483:Base Sequence; D002148:Calmodulin-Binding Proteins / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D002502:Centrioles / Q000378:metabolism; D002923:Cilia / Q000235:genetics* / Q000473:pathology / Q000502:physiology* / Q000648:ultrastructure; D004817:Epidermis / Q000196:embryology / Q000473:pathology; D005260:Female; D007246:Infertility / Q000235:genetics / Q000503:physiopathology; D007619:Kartagener Syndrome / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009024:Morphogenesis / Q000235:genetics*; D010641:Phenotype; D012137:Respiratory System / Q000473:pathology / Q000503:physiopathology; D016019:Survival Analysis; D014982:Xenopus laevis / Q000196:embryology
chemical_list: D002148:Calmodulin-Binding Proteins; D035683:MicroRNAs; C000589387:Ccp110 protein, Mouse; C551848:MIRN34a microRNA, mouse; C538721:Mirn449 microRNA, mouse