Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Caenorhabditis elegans / metabolism
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Caenorhabditis elegans / physiology*
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Caenorhabditis elegans Proteins / biosynthesis
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / metabolism
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Cell Movement*
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Epidermis / metabolism*
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Glycosylation
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Glycosyltransferases / metabolism
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Glypicans / biosynthesis
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Glypicans / genetics
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Heparan Sulfate Proteoglycans / biosynthesis*
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Heparan Sulfate Proteoglycans / genetics
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MicroRNAs / genetics
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MicroRNAs / physiology*
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Monosaccharide Transport Proteins / metabolism
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Neurons / physiology*
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Nucleobase, Nucleoside, Nucleotide, and Nucleic Acid Transport Proteins / metabolism
Substances
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Caenorhabditis elegans Proteins
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Glypicans
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Heparan Sulfate Proteoglycans
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LON-2 protein, C elegans
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MIRN79 microRNA, C elegans
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MicroRNAs
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Monosaccharide Transport Proteins
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Nucleobase, Nucleoside, Nucleotide, and Nucleic Acid Transport Proteins
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sqv-7 protein, C elegans
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Glycosyltransferases
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sqv-5 protein, C elegans