Inhibition of CMP-sialic acid transport by endogenous 5-methyl CMP

Nucleotide-sugar transporters (NSTs) transport nucleotide-sugar conjugates into the Golgi lumen where they are then used in the synthesis of glycans. We previously reported crystal structures of a mammalian NST, the CMP-sialic acid transporter (CST) (Ahuja and Whorton 2019). These structures elucida...

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Bibliographic Details
Published in:PloS one 2021-06, Vol.16 (6), p.e0249905-e0249905
Main Authors: Ahuja, Shivani, Cahill, James, Hartfield, Kimberly, Whorton, Matthew R
Format: Article
Language:English
Subjects:
Acids
Analysis
Biology and Life Sciences
Crystals
Cytoplasm
Deoxyribonucleic acid
DNA
DNA methylation
Editing
Enzymes
Epigenetics
Gene expression
Genetic transcription
Glycosylation
Glycosyltransferase
Golgi apparatus
Ligands
Lipids
Nucleotides
Phenols
Phosphatase
Physical Sciences
Physiology
Proteins
Research and Analysis Methods
Retention
Reviews
Ribonucleic acid
RNA
Structure
Sugar
Transportation
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Summary:Nucleotide-sugar transporters (NSTs) transport nucleotide-sugar conjugates into the Golgi lumen where they are then used in the synthesis of glycans. We previously reported crystal structures of a mammalian NST, the CMP-sialic acid transporter (CST) (Ahuja and Whorton 2019). These structures elucidated many aspects of substrate recognition, selectivity, and transport; however, one fundamental unaddressed question is how the transport activity of NSTs might be physiologically regulated as a means to produce the vast diversity of observed glycan structures. Here, we describe the discovery that an endogenous methylated form of cytidine monophosphate (m.sup.5 CMP) binds and inhibits CST. The presence of m.sup.5 CMP in cells results from the degradation of RNA that has had its cytosine bases post-transcriptionally methylated through epigenetic processes. Therefore, this work not only demonstrates that m.sup.5 CMP represents a novel physiological regulator of CST, but it also establishes a link between epigenetic control of gene expression and regulation of glycosylation.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0249905