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Pathogenic mechanism and therapeutic intervention of impaired N7-methylguanosine (m7G) tRNA modification [RNA-seq]

GSE229242 Mus musculus Expression profiling by high throughput sequencing 4 samples Submitted 2024/10/16 Platform GPL30215
Summary
The tRNA N7-methylguanosine (m7G) modification is not essential for yeast growth, but in mammals mis-regulations of tRNA m7G modification cause stem cell defect and developmental disorders. Here we found that homozygous mutated WDR4 caused microcephaly, retardation in motor coordination and spatial learning ability in mice, which mimics the symptom in human patients with WDR4 mutation. Further analysis revealed that homozygous mutation of WDR4 impaired tRNA m7G modification and reduced the translation level of genes involved in mTOR signaling pathway in mouse brain, which further caused endoplasmic reticulum (ER) stress and cell death. Our study uncovered a new layer of translation regulation mechanism mediated by tRNA m7G modification, provided strong evidence to support the important physiological function of mis-regulated tRNA modification in neuron disorders.
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Also filed as BioProject PRJNA953623 and SRA study SRP431596. Searching any of these in the dataset finder brings you back here.

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