Vollum Institute, Oregon Health & Science University, Portland, Oregon, United States of America.
PLoS One. 2021 Jun 3;16(6):e0249905. doi: 10.1371/journal.pone.0249905. eCollection 2021.
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.
核苷酸糖转运蛋白（NSTs）将核苷酸糖缀合物转运到高尔基体腔中，然后在那里用于糖链的合成。我们之前报道了哺乳动物 NST，即 CMP-唾液酸转运蛋白（CST）的晶体结构（Ahuja 和 Whorton 2019）。这些结构阐明了底物识别、选择性和转运的许多方面；然而，一个基本的未解决的问题是，NST 的转运活性如何可能受到生理调节，以产生观察到的大量聚糖结构。在这里，我们描述了发现一种内源性甲基化形式的胞苷一磷酸（m5CMP）结合并抑制 CST。细胞中 m5CMP 的存在是由于 RNA 的降解，这些 RNA 的胞嘧啶碱基通过表观遗传过程在转录后被甲基化。因此，这项工作不仅表明 m5CMP 代表 CST 的一种新型生理调节剂，而且还建立了基因表达的表观遗传控制与糖基化调节之间的联系。
