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miRNA proxy approach reveals hidden functions of glycosylation

Glycosylation, the most abundant posttranslational modification, holds an unprecedented capacity for altering biological function. Our ability to harness glycosylation as a means to control biological systems is hampered by our inability to pinpoint the specific glycans and corresponding biosyntheti...

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Autores principales: Kurcon, Tomasz, Liu, Zhongyin, Paradkar, Anika V., Vaiana, Christopher A., Koppolu, Sujeethraj, Agrawal, Praveen, Mahal, Lara K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4466752/
https://www.ncbi.nlm.nih.gov/pubmed/26015571
http://dx.doi.org/10.1073/pnas.1502076112
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author Kurcon, Tomasz
Liu, Zhongyin
Paradkar, Anika V.
Vaiana, Christopher A.
Koppolu, Sujeethraj
Agrawal, Praveen
Mahal, Lara K.
author_facet Kurcon, Tomasz
Liu, Zhongyin
Paradkar, Anika V.
Vaiana, Christopher A.
Koppolu, Sujeethraj
Agrawal, Praveen
Mahal, Lara K.
author_sort Kurcon, Tomasz
collection PubMed
description Glycosylation, the most abundant posttranslational modification, holds an unprecedented capacity for altering biological function. Our ability to harness glycosylation as a means to control biological systems is hampered by our inability to pinpoint the specific glycans and corresponding biosynthetic enzymes underlying a biological process. Herein we identify glycosylation enzymes acting as regulatory elements within a pathway using microRNA (miRNA) as a proxy. Leveraging the target network of the miRNA-200 family (miR-200f), regulators of epithelial-to-mesenchymal transition (EMT), we pinpoint genes encoding multiple promesenchymal glycosylation enzymes (glycogenes). We focus on three enzymes, beta-1,3-glucosyltransferase (B3GLCT), beta-galactoside alpha-2,3-sialyltransferase 5 (ST3GAL5), and (alpha-N-acetyl-neuraminyl-2,3-beta-galactosyl-1,3)-N-acetylgalactosaminide alpha-2,6-sialyltransferase 5 (ST6GALNAC5), encoding glycans that are difficult to analyze by traditional methods. Silencing these glycogenes phenocopied the effect of miR-200f, inducing mesenchymal-to-epithelial transition. In addition, all three are up-regulated in TGF-β–induced EMT, suggesting tight integration within the EMT-signaling network. Our work indicates that miRNA can act as a relatively simple proxy to decrypt which glycogenes, including those encoding difficult-to-analyze structures (e.g., proteoglycans, glycolipids), are functionally important in a biological pathway, setting the stage for the rapid identification of glycosylation enzymes driving disease states.
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spelling pubmed-44667522015-06-18 miRNA proxy approach reveals hidden functions of glycosylation Kurcon, Tomasz Liu, Zhongyin Paradkar, Anika V. Vaiana, Christopher A. Koppolu, Sujeethraj Agrawal, Praveen Mahal, Lara K. Proc Natl Acad Sci U S A Biological Sciences Glycosylation, the most abundant posttranslational modification, holds an unprecedented capacity for altering biological function. Our ability to harness glycosylation as a means to control biological systems is hampered by our inability to pinpoint the specific glycans and corresponding biosynthetic enzymes underlying a biological process. Herein we identify glycosylation enzymes acting as regulatory elements within a pathway using microRNA (miRNA) as a proxy. Leveraging the target network of the miRNA-200 family (miR-200f), regulators of epithelial-to-mesenchymal transition (EMT), we pinpoint genes encoding multiple promesenchymal glycosylation enzymes (glycogenes). We focus on three enzymes, beta-1,3-glucosyltransferase (B3GLCT), beta-galactoside alpha-2,3-sialyltransferase 5 (ST3GAL5), and (alpha-N-acetyl-neuraminyl-2,3-beta-galactosyl-1,3)-N-acetylgalactosaminide alpha-2,6-sialyltransferase 5 (ST6GALNAC5), encoding glycans that are difficult to analyze by traditional methods. Silencing these glycogenes phenocopied the effect of miR-200f, inducing mesenchymal-to-epithelial transition. In addition, all three are up-regulated in TGF-β–induced EMT, suggesting tight integration within the EMT-signaling network. Our work indicates that miRNA can act as a relatively simple proxy to decrypt which glycogenes, including those encoding difficult-to-analyze structures (e.g., proteoglycans, glycolipids), are functionally important in a biological pathway, setting the stage for the rapid identification of glycosylation enzymes driving disease states. National Academy of Sciences 2015-06-09 2015-05-26 /pmc/articles/PMC4466752/ /pubmed/26015571 http://dx.doi.org/10.1073/pnas.1502076112 Text en Freely available online through the PNAS open access option.
spellingShingle Biological Sciences
Kurcon, Tomasz
Liu, Zhongyin
Paradkar, Anika V.
Vaiana, Christopher A.
Koppolu, Sujeethraj
Agrawal, Praveen
Mahal, Lara K.
miRNA proxy approach reveals hidden functions of glycosylation
title miRNA proxy approach reveals hidden functions of glycosylation
title_full miRNA proxy approach reveals hidden functions of glycosylation
title_fullStr miRNA proxy approach reveals hidden functions of glycosylation
title_full_unstemmed miRNA proxy approach reveals hidden functions of glycosylation
title_short miRNA proxy approach reveals hidden functions of glycosylation
title_sort mirna proxy approach reveals hidden functions of glycosylation
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4466752/
https://www.ncbi.nlm.nih.gov/pubmed/26015571
http://dx.doi.org/10.1073/pnas.1502076112
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