Publikationsdatum:
2014-06-06
Beschreibung:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4119886/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4119886/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Song, Rui -- Walentek, Peter -- Sponer, Nicole -- Klimke, Alexander -- Lee, Joon Sub -- Dixon, Gary -- Harland, Richard -- Wan, Ying -- Lishko, Polina -- Lize, Muriel -- Kessel, Michael -- He, Lin -- 1R21CA175560-01/CA/NCI NIH HHS/ -- GM42341/GM/NIGMS NIH HHS/ -- R01 CA139067/CA/NCI NIH HHS/ -- R01 GM042341/GM/NIGMS NIH HHS/ -- England -- Nature. 2014 Jun 5;510(7503):115-20. doi: 10.1038/nature13413.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Division of Cellular and Developmental Biology, MCB Department, University of California at Berkeley, Berkeley, California 94705, USA [2]. ; 1] Division of Genetics, Genomics and Development, Centre for Integrative Genomics, MCB Department, University of California at Berkeley, Berkeley, California 94705, USA [2]. ; Department of Molecular Cell Biology, Max Planck Institute for Biophysical Chemistry, Goettingen 37077, Germany. ; Division of Cellular and Developmental Biology, MCB Department, University of California at Berkeley, Berkeley, California 94705, USA. ; Division of Genetics, Genomics and Development, Centre for Integrative Genomics, MCB Department, University of California at Berkeley, Berkeley, California 94705, USA. ; The Third Military Medical University, Chongqing 400038, China. ; Department of Molecular Oncology, University of Goettingen, Goettingen 37073, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24899310" target="_blank"〉PubMed〈/a〉
Schlagwort(e):
Animals
;
Animals, Newborn
;
Basal Bodies/metabolism/pathology/ultrastructure
;
Base Sequence
;
Calmodulin-Binding Proteins/*deficiency/*genetics/metabolism
;
Centrioles/metabolism
;
Cilia/*genetics/pathology/*physiology/ultrastructure
;
Epidermis/embryology/pathology
;
Female
;
Infertility/genetics/physiopathology
;
Kartagener Syndrome/genetics/pathology/physiopathology
;
Male
;
Mice
;
Mice, Knockout
;
MicroRNAs/*genetics/metabolism
;
Morphogenesis/*genetics
;
Phenotype
;
Respiratory System/pathology/physiopathology
;
Survival Analysis
;
Xenopus laevis/embryology
Print ISSN:
0028-0836
Digitale ISSN:
1476-4687
Thema:
Biologie
,
Chemie und Pharmazie
,
Medizin
,
Allgemeine Naturwissenschaft
,
Physik
