Discovery of micropeptides in human immune cells and systemic lupus erythematosus

Somewhere between 5 and 8% of the human genome is made up of viral trash: old pieces of viral genomes that once, long ago in evolution, infected our cells and left their DNA sequences behind like graffiti tags. Although these sequences, known as endogenous retroviruses, no longer code for the viral proteins they were once intended to build, they aren’t just inert stretches of our genome. Endogenous retroviruses have been implicated in our genome’s evolution and in various diseases, including lupus, a devastating autoimmune disease in which a patient’s immune system attacks their own organs. Sarah Slavoff, Ph.D., Grace Chen, Ph.D. and Joseph Craft, M.D. are leading a project to explore the hypothesis that human endogenous retroviruses produce tiny difficult-to-detect proteins known as micropeptides that could drive lupus. The team will look for the presence of micropeptides from these retroviruses in human immune cells and then will study blood samples from lupus patients to determine if their levels or roles change between healthy immune cells and those in autoimmune disease. Their work could uncover the reasons for a heretofore mysterious disease.

This project is part of the 2021 Micropeptides and immunity cohort

Our genomes contain vast amounts of DNA that remain poorly understood. A recent arrival on the scene of genomic “dark matter”: micropeptides, tiny proteins coded by tiny genes that had long escaped notice due to their size but that appear to be present in large numbers in our genome and that of every other living thing. These small molecules likely play roles in many different biological processes; scientists are recently uncovering their influence in several different diseases and in the function of the immune system. Scientists in the Micropeptides cohort are shedding new light on how micropeptides influence immunology, in health and in disease.