Excess RNA Starves Cells of Energy, Texas A&M Scientists Discover

Scientists at the Texas A&M College of Veterinary Medicine and Biomedical Sciences discovered that an excessive accumulation of RNA, including messenger RNA (mRNA), can directly impair mitochondria, starving cells of energy[1][2][3]. This finding, published in the Proceedings of the National Academy of Sciences, offers new understanding into how viral infections and aging-related diseases cause cellular damage[1][4].

The discovery holds implications for understanding diseases where excess RNA is observed, such as certain viral infections, aging-related conditions, neurodegenerative diseases, and some cancers[1][4][7]. It also influences the safety assessment and development of RNA-based therapeutics, including mRNA vaccines[6][7].

The Discovery

The research, led by Dr. Zhilong Yang, a professor in the VMBS’s Department of Veterinary Pathobiology, and involving Dr. Djamal Brahim Belhaouari, focused on the mitochondria, which generate most of a cell's energy[2][6][12]. The Texas A&M team found that when excess RNA builds up inside cells, particularly during poxvirus infection, it directly disrupts these critical energy-producing structures[3][6]. This disruption affects the electrical and chemical gradients across the inner mitochondrial membranes, which are essential for cellular respiration and energy production[3][7]. Consequently, cells are left with insufficient adenosine triphosphate (ATP) to perform their vital functions, such as growth and repair[3][11].

Unpacking the Mechanism

Dr. Yang stated that RNA degradation helps cells maintain the energy needed for proper function[6][7]. Normally, degradation systems prevent harmful levels of RNA from accumulating[6][11]. However, when RNA disposal mechanisms cannot keep pace, the surplus material interferes with mitochondrial function, causing an ATP shortage[6][11]. The study used poxviruses, such as the vaccinia virus (VACV), and observed that impaired RNA degradation in VACV-infected cells significantly compromised mitochondrial function, including cellular respiration[12][13]. The findings emphasize the importance of functional RNA degradation in protecting mitochondrial integrity during viral infections[12]. The National Institute of Allergy and Infectious Diseases and Texas A&M University supported the research[12].

Broader Relevance

This breakthrough provides a clearer understanding of how certain viral infections cause cellular damage and contribute to the progression of aging-related diseases[1][2][7]. It also helps scientists better understand how cells respond to RNA-based medicines[7]. The study expands the known critical roles of RNA degradation beyond controlling protein production and quality control, establishing it as a key factor in maintaining cellular energy balance and protecting mitochondrial health[6][7].

What We Could Not Confirm

We could not confirm if the amount of excess RNA required to cause mitochondrial damage in a living organism is equivalent to the levels observed in the laboratory experiments.