A pioneering study has illuminated the essential function of a tRNA methylation enzyme, TRMT10A, in maintaining brain health. The research indicates that a lack of TRMT10A leads to a decrease in certain transfer RNA (tRNA) types, which disrupts protein production in the brain and negatively affects the structure and operation of synapses.
A pioneering study conducted by a research team from Kumamoto University has illuminated the essential function of a tRNA methylation enzyme, TRMT10A, in maintaining brain health. The research indicates that a lack of TRMT10A leads to a decrease in certain transfer RNA (tRNA) types, which disrupts protein production in the brain and negatively affects the structure and operation of synapses.
The research team generated mice that were missing the Trmt10a gene and analyzed tRNA levels in their brains. They found a notable drop in two kinds of tRNA: the initiator methionine tRNA, which is crucial for initiating protein synthesis, and a specific glutamine tRNA. This reduction in tRNA resulted in lower protein synthesis for vital genes in the brain, particularly those related to neuronal functions. As a result, the structural stability and adaptability of synapses—which are vital for learning and memory—were affected, leading to reduced cognitive performance in the mice.
Interestingly, while a decrease in initiator methionine and glutamine tRNA levels was noted across various tissues, the functional impairments were specific to the brain, suggesting that it is especially susceptible.
Lecturer Takeshi Chujo from the Faculty of Life Sciences at Kumamoto University, who led the study, remarked: “Since human cells lacking TRMT10A showed similar reductions in these tRNA levels, it implies that the mechanisms we identified in mice may also be relevant to humans.”
The research underscores the significance of a universal tRNA modification for the translation of specific codons. With these findings, the research team intends to investigate whether preventing the decline of tRNA levels in the brain could alleviate functional deficits, potentially paving the way for new therapeutic strategies to address intellectual disabilities stemming from tRNA modification issues.
This study not only deepens our comprehension of RNA modification-related illnesses but also offers new avenues for tackling cognitive difficulties associated with these disorders.
