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Newly Discovered Glycosylated RNA Is All Over Cells

The emergence of nucleic acids and that of proteins have sometimes been called the first and second evolution revolutions, as they made life as we know it possible. Some experts argue that glycosylation—the addition of glycans to other biopolymers—should be considered the third, because it allowed cells to build countless molecular forms from the same DNA blueprints. It’s long been believed that only proteins and lipids receive these carbohydrate constructs, but a May 17 paper in Cell that builds upon a 2019 bioRxiv preprint posits that RNAs can be glycosylated, too, and these sugar-coated nucleic acids seem to localize to cell membranes.

Anna-Marie Fairhurst, who studies autoimmunity at the Agency for Science, Technology and Research in Singapore, describes the study as exciting. “Obviously, it’s the first time ever that we’ve seen this with RNA,” she says, adding that the diversity of methods used to demonstrate the presence of glycoRNAs makes the findings especially robust.

What really intrigues her are the parts present in the 2021 Cell paper that aren’t in the 2019 preprint—in particular, that glycoRNAs appear to predominantly end up on the cell’s outer membrane. There, they can attach to two kinds of sialic acid-binding immunoglobulin-type lectins (Siglecs)—a family of immune receptors implicated in several diseases, including systemic lupus erythematosus (SLE). All of this suggests glycoRNAs may play a role in immune signaling. “It’s a really exciting era of science,” Fairhurst says.

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