Slightly-known RNA molecule found only in women may influence immunity, infection severity, and autoimmune risk.
Some RNA molecules once dismissed as genetic mistakes may actually perform essential jobs in healthy cells. New research suggests that one such molecule, found only in women, could influence immune function, blood cell development, and the body’s response to disease.
Researchers at the University of Virginia School of Medicine identified a chimeric RNA called UBA1-CDK16. Chimeric RNAs contain material from more than one gene and were historically associated with cancer, where disrupted genetic processes can produce unusual molecular combinations. Scientists are now finding that some of these molecules may also be part of normal human biology.
Hui Li, PhD, and his colleagues found evidence that UBA1-CDK16 helps regulate blood cell formation and may affect the severity of illnesses such as COVID-19. Because the RNA can be detected in blood, it could eventually help researchers develop tests to diagnose disease or identify women who face a greater risk of serious complications.
“Chimeric RNAs are RNA molecules composed of parts from different genes,” said Li, of UVA’s Department of Pathology and the UVA Comprehensive Cancer Center. “They were once believed to be cancer-specific. However, our research shows that they can also be part of normal physiology and play important roles in human health.”
Rethinking Chimeric RNA
RNA carries genetic instructions that cells use to perform essential functions. Those instructions come from DNA inherited from our parents.
For years, scientists viewed chimeric RNAs as cellular errors because they combine material from separate genes. That assumption helped link them to cancer, which can develop when mistakes occur as cells copy and use genetic information.
The new research suggests that UBA1-CDK16 may contribute to women’s health by helping regulate the immune system. It appears only in women because women typically have two X chromosomes, while men typically have one X chromosome and one Y chromosome.
In female cells, one X chromosome is usually inactive. Li found that this inactive chromosome still produces UBA1-CDK16, which researchers were able to detect in women’s blood.
Li believes UBA1-CDK16 helps control the formation of blood cells. The findings also indicate that it may affect how the immune system responds to infection.
The RNA was absent in 50% of women who developed severe COVID-19, but it remained detectable in women who had no symptoms. Lower levels of the RNA were also associated with more severe disease.
Li suspects that UBA1-CDK16 may help regulate the development of neutrophils, immune cells that provide an early response to infection. (Neutrophil count has already been identified as a way to predict how patients will fare against COVID-19.)
Expanding the Functional Genome
“As humans share a similar number of genes with fruit flies and worms, gene number does not explain why we are much more sophisticated than these lower organisms,” Li said. “We believe chimeric RNAs are another means to expand the functional genome, without an actual increase in gene number.”
The research also indicates that UBA1-CDK16 may act as a natural safeguard against excessive autoimmune activity. Women develop autoimmune disorders far more often than men, and Li is calling for further studies to clarify whether this RNA helps explain that difference.
A better understanding of its role could also reveal whether the RNA can be used to improve diagnosis, assess risk, or guide new treatments.
“This finding highlights there is another layer of control for gene expression,” Li said. “These chimeric RNAs may represent a hidden repertoire for biomarkers and therapy targets as well.”
Reference: “UBA1-CDK16: A female-specific chimeric RNA emerging through evolution and involved in immune regulation” by Xinrui Shi, Loryn Blackburn, Sandeep Singh, Martyna Glowczyk-Gluc, Anam Tajammal, Shafaque Zahra, Shailesh Kumar, Robert Cornelison, Chen Liang, Fujun Qin, Aiqun Liu, Shitong Lin, Yue Tang, Justin Elfman, Thomas Manley, Timothy Bullock, Doris M. Haverstick, Peng Wu and Hui Li, 29 May 2026, Science Advances.
DOI: 10.1126/sciadv.adz9784
The research was supported by the National Institutes of Health’s National Institute of General Medical Sciences, grant R01GM132128.
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