Scientists have reported on the ability of excess RNA to disrupt energy production in cells

Scientists from Texas A&M University have discovered that excessive accumulation of RNA can disrupt the functioning of mitochondria, cellular structures that ensure the production of most of the energy needed by the cell. In laboratory experiments, this effect occurred independently of the usual signaling mechanisms of innate immunity. Why a molecule necessary for life can become a source of problems and what significance it has for studying infections is in the Izvestia material.

Why do cells need to produce and destroy RNA

RNA performs several important functions. One of its variants, matrix or informational RNA, transmits instructions for protein synthesis. Proteins, in turn, are necessary for maintaining the cell structure and the course of many biochemical reactions.

Cells are constantly creating and splitting RNA. The breakdown of spent or defective molecules helps regulate protein production and prevent the accumulation of unnecessary material. According to the results of the new work, this process is also important for maintaining normal energy metabolism.

How a viral infection upsets the balance

The researchers studied cells infected with the smallpox vaccine virus, a member of the poxvirus family. During infection, a large amount of viral RNA is formed in the cell, and its removal mechanisms must cope with the increased load.

In experiments, disruption of the work of viral or cellular enzymes involved in the destruction of RNA was accompanied by a deterioration in the condition of mitochondria and a decrease in their respiratory activity. Mitochondrial respiration is a set of processes that help a cell receive energy and store it in ATP molecules.

Scientists have linked immature brain cells with impaired thinking in epilepsy

At the same time, the damaging effect was found in two varieties of RNA. One of them is double—stranded RNA, which is often formed during viral infections and can trigger protective reactions. The other is ordinary messenger RNA, which is necessary for protein synthesis. It was the second result that turned out to be unexpected: problems arose with the excessive accumulation of a molecule that is constantly present in healthy cells.

What has the experience with isolated mitochondria shown?

Initially, the authors assumed that excess RNA damages mitochondria through activation of antiviral protection. However, experiments have shown that such a reaction is not necessary for the detected effect.

Disorders also occurred before pronounced activation of immune mechanisms. Taken together, these observations indicate that excess RNA is able to affect mitochondria directly.

Scientists have recorded a decrease in the membrane potential — the difference in electrical potentials on the sides of the inner membrane of the mitochondria. Maintaining an electrochemical gradient is necessary for the synthesis of ATP. When this mechanism is disrupted, the efficiency of energy production decreases.

Exactly how RNA causes such a malfunction is still unclear. The authors suggest that negatively charged molecules can accumulate near mitochondria and affect their working conditions. This explanation has yet to be verified.

Scientists have reported on a new way to protect the brain in Alzheimer's disease

Why is it important for a virus to keep a cell functioning

The virus depends on the resources of the infected cell: they are necessary for the production of its proteins and the formation of new viral particles. Therefore, a violation of energy metabolism can interfere with the pathogen itself.

According to Yang, poxviruses use RNA destruction mechanisms that help control its quantity and keep the cell functioning during virus reproduction.

Thus, the removal of RNA can perform several tasks at once: regulate the activity of genes, limit the recognition of infection by protective systems, and conserve the energy resources of the infected cell.

How is the discovery related to diseases and RNA drugs

The authors admit that the identified mechanism may have significance beyond viral infections. Accumulation of RNA is observed in some oncological, neurodegenerative, and aging-related conditions. However, it is not yet known to what extent the effect found in experiments is involved in the development of these diseases.

Another area is the development of RNA drugs and vaccines. Such technologies use RNA molecules to transmit instructions to cells for the production of certain proteins. Understanding how cells process this RNA and respond to its quantity can help refine future drugs.

The work was carried out in laboratory models and does not establish that existing mRNA vaccines damage mitochondria in humans. Its main result concerns the cellular mechanism: if the removal is disrupted, excess RNA can interfere with energy production. Now the researchers have to find out under what conditions this mechanism works in the body and how it can be influenced.