title: Mapping posttranscriptional regulation of the human glycome uncovers microRNA defining the glycocode.
abstract: Cell surface glycans form a critical interface with the biological milieu, informing diverse processes from the inflammatory cascade to cellular migration. Assembly of discrete carbohydrate structures requires the coordinated activity of a repertoire of proteins, including glycosyltransferases and glycosidases. Little is known about the regulatory networks controlling this complex biosynthetic process. Recent work points to a role for microRNA (miRNA) in the regulation of specific glycan biosynthetic enzymes. Herein we take a unique systems-based approach to identify connections between miRNA and the glycome. By using our glycomic analysis platform, lectin microarrays, we identify glycosylation signatures in the NCI-60 cell panel that point to the glycome as a direct output of genomic information flow. Integrating our glycomic dataset with miRNA data, we map miRNA regulators onto genes in glycan biosynthetic pathways (glycogenes) that generate the observed glycan structures. We validate three of these predicted miRNA/glycogene regulatory networks: high mannose, fucose, and terminal β-GalNAc, identifying miRNA regulation that would not have been observed by traditional bioinformatic methods. Overall, our work reveals critical nodes in the global glycosylation network accessible to miRNA regulation, providing a bridge between miRNA-mediated control of cell phenotype and the glycome.
authors.affiliation: Biomedical Chemistry Institute, Department of Chemistry, New York University, New York, NY 10003.
authors.forename: Praveen
authors.initials: P
authors.lastname: Agrawal
authors.forename: Tomasz
authors.initials: T
authors.lastname: Kurcon
authors.forename: Kanoelani T
authors.initials: KT
authors.lastname: Pilobello
authors.forename: John F
authors.initials: JF
authors.lastname: Rakus
authors.forename: Sujeethraj
authors.initials: S
authors.lastname: Koppolu
authors.forename: Zhongyin
authors.initials: Z
authors.lastname: Liu
authors.forename: Bianca S
authors.initials: BS
authors.lastname: Batista
authors.forename: William S
authors.initials: WS
authors.lastname: Eng
authors.forename: Ku-Lung
authors.initials: KL
authors.lastname: Hsu
authors.forename: Yaxuan
authors.initials: Y
authors.lastname: Liang
authors.forename: Lara K
authors.initials: LK
authors.lastname: Mahal
mesh_terms: D053898:Biosynthetic Pathways / Q000235:genetics*; D015153:Blotting, Western; D002460:Cell Line; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics / Q000502:physiology*; D053263:Gene Regulatory Networks / Q000235:genetics*; D054794:Glycomics / Q000379:methods; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D008156:Luciferases; D035683:MicroRNAs / Q000378:metabolism* / Q000494:pharmacology; D046228:Microarray Analysis; D008856:Microscopy, Fluorescence; D011134:Polysaccharides / Q000096:biosynthesis*; D060888:Real-Time Polymerase Chain Reaction; D049490:Systems Biology / Q000379:methods
chemical_list: D035683:MicroRNAs; D011134:Polysaccharides; D008156:Luciferases
keywords: NCI-60; carbohydrate biosynthesis; epigenetics; glycan regulation; systems biology