The human body has to protect itself from pathogens and infectious agents, and there are a variety of ways for the immune system to sense foreign invaders, and react to the threats they may pose. But the body also has to disregard the tissues, cells, and molecules of the self, so they do not trigger aberrant immune responses. Scientists have now identified a chemical modification that happens on RNA molecules, which prevents the immune system from reacting to that RNA.
RNA is a crucial molecule that delivers information from the genome to cells; usually, that information is instructions on how to make proteins, which carry out many cellular functions. After being copied from DNA, RNA molecules often undergo many modifications, including the addition of chemical tags. Glycosylation is one example of an RNA modification, in which a carbohydrate or glycan is attached to another molecule–in this case, RNA.
A chemical change known as N-glycosylation appears to modify some of the body's own RNA molecules so that the immune system does not react to them. This modification is a process called sialylation. It adds sialic acid-containing N-linked glycans to small RNA molecules to create glycoRNAs. These glycoRNAs can move to the surface of cells, and hang out there without triggering responses from the immune system.
"We wanted to better understand the significance of glycoRNAs," said study co-leader Ryan Flynn, MD, Ph.D. of Boston Children's Hospital. "Why does RNA undergo glycosylation in the first place and what prevents glycoRNAs from activating an immune response?"
The investigators determined that the N-glycans found on glycoRNAs work to stop the immune system from responding to the glycoRNAs. The N-glycans can hide a feature in RNA called acp3U, which can usually trigger an immune response. The findings have been reported in Nature.
This work can explain how glycoRNAs can remain on cell surfaces without causing an autoimmune reaction.
Innate immune responses that sense RNA have been implicated in some autoimmune disease like lupus. So this work could provide new insights into how glycoRNAs may be related to autoimmune disorders.
Sources: Children's Hospital Boston, Nature
