Researchers at Stanford University have discovered sugar-bound RNA strands protruding from the cell surface, challenging the long-held assumption that these two types of molecules are kept separate within the cell. These newfound “glycoRNAs,” identified by former Damon Runyon Fellow Ryan Flynn, MD, PhD, may serve an important role in immune signaling. A shock to biologists across disciplines, this finding has particular significance in the world of cancer research, as the development of effective immunotherapies hinges on our understanding of how the immune system is activated.
Glycans, or sugar chains, are known to bind to proteins and lipids to form “glycoproteins” and “glycolipids,” respectively. These compounds make their way through the cell membrane and present themselves to receptors on the surface of other cells. Because glycans are processed in a cellular compartment known as the Golgi body, there was no reason to expect that they would have any interaction with RNA, which travels from the nucleus directly to the cytoplasm.
When Dr. Flynn joined the Stanford lab as a Damon Runyon Fellow in 2017, he was focused on RNA. After learning more about role of glycans in cell communication, however, he decided to check if any of these sugars were attached to RNA molecules. Strangely, experiment after experiment turned up evidence of glycoRNAs in the Golgi body, where RNA had never before been found. A battery of tests confirmed the presence of glycoRNAs in “every type of cell [Dr. Flynn] could grow,” not only in the Golgi bodies but embedded in cell membranes.
Separately, researchers in his lab were studying “Siglecs,” receptors on the surface of immune cells that bind to glycans and thereby inhibit immune attack on the body’s own cells. Suspecting that Siglecs may also bind to glycoRNAs, Dr. Flynn tested a variety of Siglecs and found that some of them did. This finding suggests that glycoRNAs may help their host cells signal “don’t attack” to immune cells. As cancer cells often exploit such signaling mechanisms to avoid immune system capture, this could have major implications in the search for immunotherapy targets.
But first, Dr. Flynn says, “scientists have much more to learn” about the role of glycoRNAs in immune system regulation. He is now running his own lab at Harvard to pursue this line of inquiry.
This research was published in Cell.
