Pedersen, Mikael Egebjerg3; Snieckute, Goda3; Kagias, Konstantinos3; Nehammer, Camilla3; Multhaupt, Hinke A B4; Couchman, John R4; Pocock, Roger3
1 Pocock Group, BRIC Research Groups, BRIC, Københavns Universitet2 Section of Molecular Pathology, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, Københavns Universitet3 Pocock Group, BRIC Research Groups, BRIC, Københavns Universitet4 Section of Molecular Pathology, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, Københavns Universitet
An appropriate balance in glycosylation of proteoglycans is crucial for their ability to regulate animal development. Here, we report that the Caenorhabditis elegans microRNA mir-79, an ortholog of mammalian miR-9, controls sugar-chain homeostasis by targeting two proteins in the proteoglycan biosynthetic pathway: a chondroitin synthase (SQV-5; squashed vulva-5) and a uridine 5'-diphosphate-sugar transporter (SQV-7). Loss of mir-79 causes neurodevelopmental defects through SQV-5 and SQV-7 dysregulation in the epidermis. This results in a partial shutdown of heparan sulfate biosynthesis that impinges on a LON-2/glypican pathway and disrupts neuronal migration. Our results identify a regulatory axis controlled by a conserved microRNA that maintains proteoglycan homeostasis in cells.