RNA is usually described as the cell’s messenger, the molecule that carries instructions from DNA so proteins can be built. A new study suggests it also has a less obvious side: when RNA piles up faster than the cell can clear it, it can interfere with the cell’s power plants.

Researchers at the Texas A&M University College of Veterinary Medicine and Biomedical Sciences report that excess RNA can impair mitochondria, the structures that generate most of a cell’s energy. The work, published in Proceedings of the National Academy of Sciences, looked at cells infected with poxviruses, the virus family that includes smallpox and mpox.

The balancing act inside an infected cell

Cells constantly make RNA and constantly break it down. That degradation was already known to help regulate protein production, remove faulty RNA and shape immune responses. This study points to one more job: protecting the cell’s ability to produce energy.

Viruses complicate the picture. They depend entirely on the host cell for energy and protein production, yet they also flood it with viral RNA. According to the researchers, poxviruses appear to use the cell’s RNA cleanup systems to degrade RNA and keep the host cell functioning long enough to keep replicating. A cell that is too damaged is a poor factory for making new virus.

Not just an immune reaction

Double-stranded RNA, which viruses commonly produce, is a well-known alarm signal for the immune system. The team first suspected that the mitochondrial damage came from that immune response. The data pointed elsewhere. When they isolated mitochondria and added RNA directly, the mitochondria were still damaged. The impairment also appeared before major immune responses kicked in and did not depend on the usual immune pathways.

The surprise was that the effect was not limited to double-stranded RNA. Excess messenger RNA, a normal and necessary molecule, could also harm mitochondria.

How this happens is not yet known. The authors offer a tentative idea: because RNA carries a negative charge, it may gather around mitochondria and disturb the electrical balance those organelles rely on to make energy. They describe this as a new concept they are still testing.

Why it might matter beyond viruses

RNA accumulation has been observed in some cancers, neurodegenerative diseases and age-related disorders. The researchers suggest mitochondrial damage could be one way excess RNA contributes to such conditions. They also say that understanding how cells respond to large amounts of RNA could eventually help in designing and optimizing RNA-based therapeutics and vaccines.

What to keep in mind

  • The experiments centered on poxvirus infection. Links to cancer, aging and neurodegeneration are proposed implications, not demonstrated results.
  • The mechanism of mitochondrial damage is still unknown.
  • The comments about RNA therapeutics and vaccines are about future research directions. The press release does not report any problem with existing RNA-based products.

Sources: