Methylated eEF1A selectively decodes mRNA to shape cancer proteomes.

METTL13-catalysed eEF1A lysine 55 dimethylation (eEF1AK55me2) enhances decoding of select codons, boosting pro-oncogenic protein synthesis linked to tumorigenesis and KRAS-inhibitor resistance.

• Why it matters: mRNA decoding efficiency shapes protein output, but it was unclear whether translation elongation itself contains intrinsic, selective mechanisms that tune proteomes in cancer.
• What they did: Using proteomic profiling and single-molecule imaging, the study tested how eEF1AK55me2 affects decoding efficiency, then applied METTL13 knockdown and synonymous recoding in cancer cells and tumour models.
• The result: METTL13 loss reduced translation of oncogenic mRNAs enriched in eEF1AK55me2-dependent codons, including KRAS, and inhibited growth of sotorasib-resistant lung adenocarcinoma tumours; in relapsed autochthonous KRAS G12C-driven disease, METTL13 ablation mitigated resistance, extended survival, and inferred METTL13 activity associated with inferior clinical response.

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