TRMT10A, short for tRNA methyltransferase 10A, is responsible for N1-methylguanosine modification at position nine of various cytoplasmic tRNAs in higher eukaryotes [1,6]. This modification is crucial for maintaining the normal function of tRNAs, which are essential for protein synthesis. It may also be involved in pathways related to mitochondrial and glucose metabolism [2].

Trmt10a null mice showed a universal decrease in tRNAGln(CUG) and initiator methionine tRNA levels in various tissues, similar to human cell lines lacking TRMT10A. Ribosome profiling of mouse brain revealed that TRMT10A dysfunction causes ribosome slowdown at the Gln(CAG) codon and increased translation of Atf4. In the mutant brain, the translation of a subset of mRNAs, especially those for neuronal structures, is perturbed. Despite no discernable defects in the pancreas, liver, or kidney, Trmt10a null mice had lower body weight, smaller hippocampal postsynaptic densities, defective synaptic plasticity, and memory [1].

In conclusion, TRMT10A plays a vital role in maintaining normal tRNA function and levels, especially for tRNAGln and initiator methionine tRNAs. Through gene-knockout mouse models, it has been revealed that TRMT10A is crucial for normal brain functions, including synaptic plasticity and memory. Dysfunction of TRMT10A is associated with various human diseases such as intellectual disability, microcephaly, diabetes, and short stature [1,2,3,4,5,7].