UC San Diego scientists studying transfer RNAs in cells have found a mutation in a gene that could impact how brain cells operate and even alter brain function and behavior, it was announced Thursday.
The scientists said the mutation — in a gene called n-Tr20 — can potentially disrupt transmissions in the brain, something which has been implicated in past studies to play a role in neurological diseases, including epilepsy and autism spectrum disorders. Their research was published this week in the journal Neuron.
Transfer RNAs, or tRNAs, play a role in cells as the “messenger” for DNA to create vital proteins. They are plentiful in cells, and hundreds of tRNA genes exist in mammalian cells. Yet, according to the study’s first author Mridu Kapur, they are often not considered in the search for the roots of disease processes.
“tRNAs have generally been overlooked in the hunt for the genetic causes of disease, but recent whole-genome sequencing projects have revealed that there are many variations in tRNA sequences in the human population,” said Kapur, a postdoctoral scholar working in neuroscience professor Susan Ackerman’s laboratory. “Our study suggests the enormous potential for tRNA variants to contribute to disease outcomes and phenotypic variability.”
The researchers found that a loss of n-Tr20, one of the members of a five-gene tRNA family, made mice resistant to seizures. The results confirm their speculations that tRNA mutations can influence other mutations and indicate that these mutations alone can also alter brain function.
“You can imagine it’s like a seesaw — if you push either way you can have problems,” said Ackerman, a member of the section of neurobiology at the Howard Hughes Medical Institute. “Keeping balance of these two opposing forces is essential for normal function. Shifting one way or another can lead to neurological diseases. It’s becoming well accepted in the autism spectrum disorder field that what we are really seeing is an imbalance of excitatory/inhibitory neurotransmission.”
Ackerman said part of the reason tRNAs have been overlooked in disease investigations is because researchers commonly concentrate on mutations in unique genes. A member of a large family such as n-Tr20 typically gets tossed in the genetic garbage can because they are too similar to one other.
“We never knew a mutation in a multi-copy tRNA gene could do anything like this,” Ackerman said. “These findings make you think about people who have diseases with variable symptoms and how much this class of overlooked genes could be playing a role in their disease. So we’re seeing this go from a behavior, such as seizure, all the way to the molecular underpinnings causing them.”
The researchers said the findings are “likely the tip of the iceberg,” and they intend to turn their attention to studying tRNA links to disease in tissues outside the brain.
— City News Service
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