A team of scientists at Texas A&M University discovered that excess RNA can disrupt the machinery cells use to produce energy, even without activating the immune defenses researchers initially suspected were responsible.
The findings, published in the Proceedings of the National Academy of Sciences in May 2026, emerged from experiments involving poxvirus infections and mitochondria, the structures responsible for much of a cell’s energy production. The discovery reveals an unexpected complication for viruses, which depend on functioning cells to reproduce but can generate RNA that interferes with those same cells.
The research raises questions about how cells manage RNA, a molecule essential for protein production and normal biological functions.
The findings suggest that removing excess RNA may help protect the cellular machinery responsible for energy production.
Researchers Find Excess RNA Can Damage Mitochondria
The scientists found that mitochondrial impairment could occur without activating the immune responses they initially suspected. Their investigation focused on RNA accumulation during infection with vaccinia virus, a poxvirus.
The scientists investigated RNA accumulation during infection with vaccinia virus, a poxvirus that also includes the viruses responsible for smallpox and mpox.
Certain RNA molecules can activate antiviral defenses during infection. Researchers examined whether those responses explained the mitochondrial problems they observed.
However, mitochondrial impairment occurred before substantial immune activation and did not depend on the interferon and protein kinase R pathways examined in the study.
The team then isolated mitochondria from cells and exposed them directly to RNA. Even without the surrounding cellular machinery, mitochondrial respiration declined.
“When we isolated only the mitochondria and added RNA, we still saw mitochondrial damage,” said Dr. Djamal Brahim Belhaouari, the study’s first author, in a Texas A&M University report.
The experiment strengthened evidence that excessive RNA can directly interfere with mitochondrial function.
Mitochondria generate much of the adenosine triphosphate (ATP) that cells use for energy. Researchers also observed changes in mitochondrial membrane potential, an electrical difference essential to that process.
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Excess RNA Disrupts More Than Infected Cells
The researchers found that mitochondrial impairment wasn’t limited to double-stranded RNA associated with viral infections. Messenger RNA, which cells normally use to produce proteins, also disrupted mitochondrial respiration when introduced in excessive amounts.
Double-stranded RNA can appear during viral replication and activate cellular defenses. Messenger RNA, by contrast, carries genetic instructions cells use to manufacture proteins.
Both forms impaired mitochondrial respiration when introduced in excessive amounts during laboratory experiments.
This suggested that RNA accumulation itself, rather than simply the immune response it might trigger, could influence cellular energy production.
Scientists have not established precisely how the interaction occurs. One hypothesis suggests that RNA’s negative electrical charge could disrupt the electrical conditions mitochondria need to function.
The findings were published May 26, 2026, in the peer-reviewed journal Proceedings of the National Academy of Sciences. The research was conducted by scientists affiliated with Texas A&M University and Kansas State University.
The authors are Djamal Brahim Belhaouari, Anil Pant, Santiago Navarro-Forero, Fernando Cantu, and Zhilong Yang, affiliated with Texas A&M University and Kansas State University.
The Discovery Explains Why Viruses Must Regulate RNA
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The findings also reveal a challenge viruses face when reproducing inside living cells. Although viruses can disrupt normal cellular processes, they still depend on functioning host cells to multiply.
Viruses rely on cellular machinery to manufacture the components needed to multiply. However, during infection, excessive RNA production can disrupt normal cellular activity.
Poxviruses use RNA degradation mechanisms to regulate RNA accumulation inside infected cells.
According to Dr. Zhilong Yang, a professor of veterinary pathobiology at Texas A&M, maintaining that balance matters because viral replication depends on the host cell’s condition. “If the cell is not healthy, the virus would not replicate well,” Yang explained in the university’s reporting.
The relationship reveals a biological tension. Although infection can damage cells, viruses also depend on the continued functioning of the cellular systems they exploit.
The research suggests RNA degradation helps maintain those conditions during poxvirus infection, although it does not establish that all viruses use the same mechanism.
The Findings Raise New Questions About Human Diseases
The discovery could help researchers investigate how abnormal RNA accumulation affects cellular function beyond viral infections. Scientists must now determine whether the mitochondrial effects observed in laboratory experiments also occur in living human tissues.
Abnormal RNA accumulation has been associated with certain cancers, neurodegenerative conditions, and biological processes linked to aging. The findings offer researchers another possible direction for investigating how RNA regulation affects mitochondrial function.
However, the experiments do not establish that this mechanism causes any particular human disease.
The results may also inform future investigations involving RNA-based medicines, including treatments that use messenger RNA. Importantly, the study did not demonstrate that existing mRNA vaccines damage mitochondria in vaccinated people.
Further experiments are needed to determine whether the laboratory findings apply to living human tissues and what RNA amounts could produce similar effects under different conditions.
For researchers, the discovery adds another dimension to a familiar biological process. Producing RNA is essential to cellular life, but understanding what happens when cells cannot remove it efficiently may be just as revealing.
If cells depend on carefully managing the molecules they produce, what else might scientists discover when that balance is disturbed?
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