Glycosylated RNA (GlycoRNAs) prior to 2019 were not known to exist. Now, researchers have found that they are present on lots of cells and may play an important role in immune signalling.
Glycans and RNA
Glycans are involved in the regulation of a range of essential cellular functions, particularly in relation to cell surface events. They modify lipids and proteins to mediate inter- and intramolecular interactions. As a result, many fundamental processes such as embryogenesis, host-pathogen recognition and tumour-immune interactions rely on glycosylation. In every cell that has been studied to date, across all domains of life, glycans have been present.
Meanwhile, RNA is another biopolymer that is central to all known life. RNAs have a complex role; serving as scaffolds, molecular decoys, enzymes and network regulators. Until now, RNA was not thought to be a major target of glycosylation.
In a recent paper, published in Cell, researchers built upon a 2019 bioRxiv preprint that posits that RNAs can also be glycosylated. The team specifically used a range of chemical and biochemical approaches to identify conserved small noncoding RNAs that harboured sialylated glycans.
Like in the 2019 study, when the team inhibited key enzymes involved in glycosylation, they found that glycoRNAs disappeared in a dose-dependent manner. The researchers also found that these glycoRNAs were present in multiple cell types and mammalian species both in cultured cells and in vivo. New data revealed that these glycoRNAs were present on the cell surface and were able to interact with anti-dsRNA antibodies.
The researchers suspected that glycoRNAs were involved in cell-to-cell signalling, particularly in an immune context. The team were previously investigating the ligands of Siglecs – a group of sugar-binding receptors that modulate immune reactions. As a result, the team conducted a series of experiments to determine whether any of these ligands bound to glycoRNAs. From this, they found that the binding of Siglec-11 and Siglec-14 dropped sharply when cells were treated with RNase. Thereby, suggesting that these ligands were cleaved from the surface.
Although many questions remain, including how glycans attach to RNAs, these findings demonstrate the existence of a direct interface between RNA biology and glycobiology. It also adds extracellular biology to the extensive role of RNAs in all living life.
Image credit: By Science Photo Library – canva.com