image: Loss of TRMT10A led to a decrease in the levels of initiator methionine tRNA (tRNAiMet) and a specific glutamine tRNA (tRNAGln). This reduction weakened the initiation of protein synthesis for certain brain genes and made the genetic code for glutamine harder to recognize. As a result, the production of neuron-related proteins was impaired, leading to brain dysfunction.
Credit: Kazuhito Tomizawa and Takeshi Chujo, Kumamoto University
A groundbreaking study conducted by a research team from Kumamoto University has shed light on the critical role of a tRNA methylation enzyme, TRMT10A, in supporting brain function. The findings reveal how the absence of TRMT10A leads to a reduction in specific transfer RNA (tRNA) levels, disrupting protein synthesis in the brain and impairing synaptic structure and function.
The research group created mice lacking the Trmt10a gene and measured tRNA levels in the brain. They discovered a significant decrease in two types of tRNA: the initiator methionine tRNA, essential for starting protein synthesis, and a specific glutamine tRNA. This reduction resulted in diminished protein synthesis of key genes in the brain, particularly those associated with neuronal function. Consequently, the structural integrity and plasticity of synapses—crucial for learning and memory—were compromised, leading to impaired cognitive abilities in the mice.
Remarkably, while a decrease in initiator methionine and glutamine tRNA levels was observed throughout various tissues, functional impairments were limited to the brain, indicating its particular vulnerability.
Lecturer Takeshi Chujo from the Faculty of Life Sciences, Kumamoto University, who led the research, stated: “Since human cells lacking TRMT10A exhibited similar reductions in these tRNA levels, it suggests that the mechanisms we discovered in mice could likely apply to humans as well.”
The study highlights the importance of a universal tRNA modification for translation of specific codons. With these insights, the research team aims to explore whether preventing the decline of tRNA levels in the brain could mitigate functional impairments, potentially leading to novel therapeutic approaches for treating intellectual disabilities caused by tRNA modification deficiencies.
This research not only enhances our understanding of RNA modification diseases but also opens doors to innovative strategies for addressing cognitive challenges linked to these conditions.
Journal
Nucleic Acids Research
Method of Research
Experimental study
Subject of Research
Animals
Article Title
TRMT10A dysfunction perturbs codon translation of initiator methionine and glutamine and impairs brain functions in mice
Article Publication Date
2-Jul-2024
COI Statement
The authors declare no conflicts of interest