Mapping posttranscriptional regulation of the human glycome uncovers microRNA defining the glycocode

Praveen Agrawal, Tomasz Kurcon, Kanoelani T. Pilobello, John F. Rakus, Sujeethraj Koppolu, Zhongyin Liu, Bianca S. Batista, William S. Eng, Ku Lung Hsu, Yaxuan Liang, Lara K. Mahal

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)4338-4343
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number11
DOIs
StatePublished - Mar 18 2014

Keywords

  • Carbohydrate biosynthesis
  • Epigenetics
  • Glycan regulation
  • NCI-60
  • Systems biology

ASJC Scopus subject areas

  • General

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