Female-Specific RNA Biomarker May Help Explain Sex Differences in Immune Disease

Women show distinct susceptibility to infectious diseases and higher rates of autoimmune disorders, yet the molecular drivers remain unclear. This gap has limited sex-specific diagnostic and prognostic tools. A new study now identifies a female-specific chimeric RNA that influences blood cell development and is associated with COVID-19 severity.

At the University of Virginia (UVA) School of Medicine, investigators identified UBA1-CDK16, a chimeric RNA found only in women. Chimeric RNAs are molecules assembled from parts of different genes rather than a single locus. UBA1-CDK16 originates from the inactive X chromosome and can be detected in women’s blood.

The team linked UBA1-CDK16 to hematopoiesis and immune regulation in women. The RNA’s female specificity reflects X-chromosome biology, with the inactive X producing this sequence despite global silencing. The authors highlight that chimeric RNAs, once regarded as cancer byproducts, can also be part of normal physiology with regulatory functions.

Findings reported that UBA1-CDK16 was absent in 50% of women who developed severe COVID-19, while it remained present in women who were asymptomatic. Lower levels of the RNA tracked with increasing infection severity. The researchers also suggest a role in governing neutrophil development, consistent with known links between neutrophil counts and COVID-19 outcomes.

The work appears in Science Advances on May 29, 2026. The study was conducted in UVA’s Department of Pathology in collaboration with the UVA Comprehensive Cancer Center. The authors add that UBA1-CDK16 may act as a natural brake on excessive autoimmune activity in women and could inform development of blood-based tests to diagnose disease or stratify risk, pending additional research.

“Chimeric RNAs are RNA molecules composed of parts from different genes. 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,” said Hui Li, Ph.D., of the Department of Pathology and the UVA Comprehensive Cancer Center, University of Virginia.

"This finding highlights that there is another layer of control for gene expression. These chimeric RNAs may represent a hidden repertoire for biomarkers and therapy targets as well," said Li.

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