tRNA-m1A methylation controls the infection of Magnaporthe oryzae by supporting ergosterol biosynthesis

Ergosterols are essential components of fungal plasma membranes. Inhibitors targeting ergosterol biosynthesis (ERG) genes are critical for controlling fungal pathogens, including Magnaporthe oryzae, the fungus that causes rice blast. However, the translational mechanisms governing ERG gene expression remain largely unexplored. Here, we show that the Trm6/Trm61 complex catalyzes dynamic N1-methyladenosine at position 58 (m1A58) in 51 transfer RNAs (tRNAs) of M. oryzae, significantly influencing translation at both the initiation and elongation stages. Notably, tRNA m1A58 promotes elongation speed at most cognate codons mainly by enhancing eEF1-tRNA binding rather than affecting tRNA abundance or charging. The absence of m1A58 leads to substantial decreases in the translation of ERG genes, ergosterol production, and, consequently, fungal virulence. Simultaneously targeting the Trm6/Trm61 complex and the ergosterol biosynthesis pathway markedly improves rice blast control. Our findings demonstrate an important role of m1A58-mediated translational regulation in ergosterol production and fungal infection, offering a potential strategy for fungicide development. [Display omitted] •The Trm6/Trm61 complex catalyzes dynamic tRNA m1A58 in Magnaporthe oryzae•tRNA m1A58 promotes elongation speed mainly by enhancing eEF1-tRNA binding•m1A58 boosts ergosterol biosynthesis gene translation, aiding M. oryzae infection•Dual targeting of m1A58 and ergosterol production improves rice blast control He et al. show that the Trm6/Trm61 complex catalyzes dynamic m1A58 methylation in tRNAs of the rice blast fungus, Magnaporthe oryzae. This modification promotes the translation of ergosterol biosynthesis genes, crucial for fungal virulence. Targeting both m1A58 methylation and ergosterol production offers an effective strategy for controlling rice blast disease.