Summary: A new research reveals that the presence of the TRMT10A protein affects tRNA levels, leading to compromised proteins production and brain function. Scientists discovered that mice lacking the Trmt10a protein had lower levels of significant tRNAs, which affected synaptic connections and mental abilities.
The findings suggest that the brain is particularly susceptible to tRNA reduction because it occurs in a variety of cells. This study could lead to the development of novel treatments for treating intellectual disability using tRNA customization.
Important Information:
- Reduction of TRMT10A reduces important ribosome levels, affecting mental protein synthesis.
- Mice lacking Trmt10a had impaired junction performance and cognitive skills.
- The research identifies the potential for novel treatments that target tRNA changes.
Origin: Kumamoto University
A breakthrough study led by a Kumamoto University research team has revealed the crucial role that a tRNA methylation enzyme, TRMT10A, plays in maintaining brain function.
The findings reveal how the absence of TRMT10A causes a drop in specific transfer RNA (tRNA ) levels, which causes a breakdown in brain protein synthesis and impairs synaptic structure and function.
The research team created animals lacking the , Trmt10a , protein and measured tRNA rates in the mind. The promoter methionine tRNA, which is necessary for the beginning of protein synthesis, and a certain glutamine tRNA were both found to be significantly lower. Important mind genes, especially those linked to cerebral function, were reduced as a result of this reduction.
Thus, the structural integrity and flexibility of synapses—crucial for teaching and memory—were compromised, leading to impaired mental powers in the animals.
Amazingly, while a decrease in promoter nucleotide and glutamine ribosome levels was observed throughout different tissues, functional impairments were limited to the brain, indicating its special vulnerability.
Lecturer Takeshi Chujo from the University of Life Sciences, Kumamoto University, who led the study, stated:” Since animal tissue lacking TRMT10A expressed similar reductions in these tRNA levels, it suggests that the mechanisms we discovered in mice could possibly apply to humans as well”.
The study emphasizes the value of a common codon modification for certain codon translation. With these findings, the research team hopes to find out whether reducing the brain’s tRNA levels may reduce functional impairments, which might lead to novel therapeutic strategies for treating intellectual impairments brought on by ribosome customization deficiencies.
This study expands our understanding of RNA-modified conditions and provides new ways to address mental issues brought on by these conditions.
About this news item about neural plasticity and genetics
Author: Nuo LI
Source: Kumamoto University
Contact: Nuo LI – Kumamoto University
Image: The image is credited to Neuroscience News
Original Research: Start exposure.
Takeshi Chujo and colleagues ‘ study,” TRMT10A dysfunction impairs brain functions in mice by altering the ribosome translation of nucleotide and glutamine.” Nucleic Acids Research
Abstract
TRMT10A function impairs mental functions in mice by altering the ribosome translation of the initiator methionine and glutamine.
In higher eukaryotes, tRNA methyltransferase 10A ( TRMT10A ) is responsible for , N1-methylguanosine modification at position nine of various cytoplasmic tRNAs.
Pathogenic mutations in , TRMT10A , produce intellectual disability, idiocy, diabetes, and small stature in humans, and create toxic tRNA fragments in cultured cells, but, it is not obvious how TRMT10A supports codon translation or brain functions.
Here, we generated , Trmt10a , null mice and showed that tRNAGln ( CUG)  , and initiator methionine tRNA levels were universally decreased in various tissues, the same was true in a human cell line lacking TRMT10A.
A mouse brain ribosome profiling revealed that TRMT10A dysfunction leads to ribosome slowdown at the Gln ( CAG ) codon and increases translation of Atf4 due to the higher frequency of leaky scanning of its upstream open reading frames.
Broadly speaking, translation of a subset of mRNAs, especially those for neuronal structures, is perturbed in the mutant brain.
Despite not showing discernable defects in the pancreas, liver, or kidney,  , Trmt10a , null mice showed lower body weight and smaller hippocampal postsynaptic densities, which is associated with defective synaptic plasticity and memory.
Our study, taken together, demonstrates the significance of universal tRNA modification during the translation of particular codons and provides mechanistic insight into the roles that TRMT10A plays in the brain.
