Department of Chemistry, Stanford University, Stanford, CA, USA.
Department of Chemistry, Stanford University, Stanford, CA, USA.
Cell. 2021 Jun 10;184(12):3109-3124.e22. doi: 10.1016/j.cell.2021.04.023. Epub 2021 May 17.
Glycans modify lipids and proteins to mediate inter- and intramolecular interactions across all domains of life. RNA is not thought to be a major target of glycosylation. Here, we challenge this view with evidence that mammals use RNA as a third scaffold for glycosylation. Using a battery of chemical and biochemical approaches, we found that conserved small noncoding RNAs bear sialylated glycans. These "glycoRNAs" were present in multiple cell types and mammalian species, in cultured cells, and in vivo. GlycoRNA assembly depends on canonical N-glycan biosynthetic machinery and results in structures enriched in sialic acid and fucose. Analysis of living cells revealed that the majority of glycoRNAs were present on the cell surface and can interact with anti-dsRNA antibodies and members of the Siglec receptor family. Collectively, these findings suggest the existence of a direct interface between RNA biology and glycobiology, and an expanded role for RNA in extracellular biology.
聚糖修饰脂质和蛋白质，介导生命所有领域的分子间和分子内相互作用。人们认为 RNA 不是糖基化的主要靶标。在这里，我们用哺乳动物将 RNA 用作糖基化的第三个支架的证据挑战了这一观点。使用一系列化学和生化方法，我们发现保守的小非编码 RNA 带有唾液酸化的聚糖。这些“糖 RNA”存在于多种细胞类型和哺乳动物物种、培养细胞和体内。糖 RNA 的组装依赖于典型的 N-聚糖生物合成机制，导致富含唾液酸和岩藻糖的结构。对活细胞的分析表明，大多数糖 RNA 存在于细胞表面，可以与抗 dsRNA 抗体和 Siglec 受体家族成员相互作用。总的来说，这些发现表明 RNA 生物学和糖生物学之间存在直接的界面，以及 RNA 在细胞外生物学中作用的扩展。
