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TRMT6-mediated tRNA m1A modification serves as a translational checkpoint of histone biosynthesis and facilitates colorectal cancer progression [RNA]

GSE233356 Homo sapiens Expression profiling by high throughput sequencing 6 samples Submitted 2025/02/08 Platform GPL24676
Summary
Reprogramming of mRNA translation drives malignant transformation and cancer development. Recently, increasing studies have demonstrated that tRNA modification emerges as a critical regulator of translational reprogramming; however, its function in cancers remains largely elusive. Herein, we identify the oncogenic role of tRNA N1-methyladenosine (m1A) modification in colorectal cancer (CRC). Targeting m1A methyltransferase TRMT6 in CRC cells decreases the abundance of a specific subset of tRNAs (e.g., tRNA-Arg-ACG-1-1, tRNA-Lys-TTT-1-1) and impairs histone mRNA translation in a codon-biased manner, thus restricting histone biosynthesis and cell cycle progression. We further demonstrate that the combination of TRMT6 inhibition and CDK4/6 inhibition shows a stronger anti-cancer effect on CRC cells by synergistically inhibit histone biosynthesis. Collectively, our study reveals that tRNA m1A modification acts as a translational checkpoint of histone biosynthesis and promotes CRC progression, providing new insights for the development of efficient therapeutic strategies against CRC.
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Also filed as BioProject PRJNA976055 and SRA study SRP439663. Searching any of these in the dataset finder brings you back here.

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