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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Autores principales:	Shivani Ahuja, James Cahill, Kimberly Hartfield, Matthew R Whorton
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dc80040564154a17b895075e23eeecd9
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spelling	oai:doaj.org-article:dc80040564154a17b895075e23eeecd92021-12-02T20:03:59ZInhibition of CMP-sialic acid transport by endogenous 5-methyl CMP.1932-620310.1371/journal.pone.0249905https://doaj.org/article/dc80040564154a17b895075e23eeecd92021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0249905https://doaj.org/toc/1932-6203Nucleotide-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 (m5CMP) binds and inhibits CST. The presence of m5CMP 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 m5CMP represents a novel physiological regulator of CST, but it also establishes a link between epigenetic control of gene expression and regulation of glycosylation.Shivani AhujaJames CahillKimberly HartfieldMatthew R WhortonPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 6, p e0249905 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shivani Ahuja James Cahill Kimberly Hartfield Matthew R Whorton Inhibition of CMP-sialic acid transport by endogenous 5-methyl CMP.
description	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 (m5CMP) binds and inhibits CST. The presence of m5CMP 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 m5CMP represents a novel physiological regulator of CST, but it also establishes a link between epigenetic control of gene expression and regulation of glycosylation.
format	article
author	Shivani Ahuja James Cahill Kimberly Hartfield Matthew R Whorton
author_facet	Shivani Ahuja James Cahill Kimberly Hartfield Matthew R Whorton
author_sort	Shivani Ahuja
title	Inhibition of CMP-sialic acid transport by endogenous 5-methyl CMP.
title_short	Inhibition of CMP-sialic acid transport by endogenous 5-methyl CMP.
title_full	Inhibition of CMP-sialic acid transport by endogenous 5-methyl CMP.
title_fullStr	Inhibition of CMP-sialic acid transport by endogenous 5-methyl CMP.
title_full_unstemmed	Inhibition of CMP-sialic acid transport by endogenous 5-methyl CMP.
title_sort	inhibition of cmp-sialic acid transport by endogenous 5-methyl cmp.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/dc80040564154a17b895075e23eeecd9
work_keys_str_mv	AT shivaniahuja inhibitionofcmpsialicacidtransportbyendogenous5methylcmp AT jamescahill inhibitionofcmpsialicacidtransportbyendogenous5methylcmp AT kimberlyhartfield inhibitionofcmpsialicacidtransportbyendogenous5methylcmp AT matthewrwhorton inhibitionofcmpsialicacidtransportbyendogenous5methylcmp
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Inhibition of CMP-sialic acid transport by endogenous 5-methyl CMP.

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