Abstract:
A latest biomedical study published in the Proceedings of the National Academy of Sciences (PNAS) reveals that excess RNA accumulation inside cells can directly damage mitochondrial function, thereby preventing cells from producing energy. This major discovery was made by a research team at Texas A&M University's School of Veterinary Medicine and Biomedical Sciences. It not only reveals a new mechanism of viral infection, but also provides a new scientific perspective for understanding the aging process and optimizing RNA-based drug therapies.
In normal cell physiological activities, messenger RNA (mRNA) is responsible for carrying genetic instructions to synthesize proteins and maintain the daily operation of cells. However, when cells are infected by members of the Poxviridae family such as smallpox virus and monkeypox virus, the virus will replicate massively inside the cell and produce huge amounts of RNA. Previous studies have generally believed that abnormal products such as double-stranded RNA are mainly used to activate the host's immune defense mechanism; but this latest research shows that even normal mRNA in cells can cause a fatal blow to cells if it accumulates excessively and cannot be degraded in time.
Experimental data show that excess RNA can directly cause physical and functional damage to mitochondria, the "energy factory" of the cell. To test whether this damage was independent of the immune system response, the researchers conducted ex vivo experiments: Adding excess RNA to an environment containing only isolated mitochondria still observed a decline in mitochondrial function. The research team speculates that this may be due to the large accumulation of negatively charged RNA molecules around mitochondria under electron microscopy, disrupting the potential balance required for energy conversion by mitochondria.
This discovery illustrates why many viruses have extremely efficient RNA-cleaning mechanisms of their own. For viruses that rely on host cells for survival, if the host cells die prematurely due to energy exhaustion, the virus's replication process will also be forced to interrupt. Therefore, the virus maintains the total amount of RNA in the cell at a dynamic equilibrium state by degrading part of its own and host RNA to ensure that the host cell can continue to provide energy support for its replication.
The researchers pointed out that this result shows that the RNA degradation mechanism inside cells not only assumes the functions of gene expression regulation and immune warning, but also is a key barrier to maintaining cellular energy metabolism balance. The confirmation of this mechanism not only helps explain why viral infection can cause severe cell damage and tissue fatigue, but also reminds the scientific community that when developing new mRNA vaccines or RNA interference therapies, the dosage must be strictly evaluated to avoid potential side effects such as cellular energy depletion caused by the artificial introduction of excess RNA.
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