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t6A tRNA modification defines RIG-I mediated anti-tumour immune response [RNA-seq1]

GSE286709 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2025/12/08 Platform GPL13112
Summary
The immune response in cancer, particularly in melanoma, is often hindered by tumour-induced immune evasion strategies, but the precise mechanisms for this remains unclear. Here, we reveal how the tRNA modification threonine-6-adenosine (t6A), mediated by O-sialoglycoprotein endopeptidase (OSGEP), maintains proteostasis in melanoma cells to prevent anti-tumour immune recognition. Cytoplasmic translation depends on the formation of t6A modification in position 37 of tRNANNU for efficient decoding of ANN codons. Defective protein homeostasis resulting from knockdown of OSGEP triggers accumulation of protein aggregates and the formation of stress granules. This disrupted codon-specific translation induces the activation of RIG-I and type I interferon response. Hence, t6A-deficient tumours prompt recruitment and activation of T-cells, affecting tumour growth. Finally, an OSGEP-driven gene signature in melanoma patients is predictive for T-cell infiltration and overall survival. Together, our results reveal t6A tRNA modification as a novel therapeutic target to fight melanoma.
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Also filed as BioProject PRJNA1209978 and SRA study SRP557064. Searching any of these in the dataset finder brings you back here.

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