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Published on: June 2, 2021
tRNA-m1A methylation controls the infection of Magnaporthe oryzae by supporting ergosterol biosynthesis
Rongrong He1, Ziwei Lv2, Yinan Li1
1National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China; College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.
Abstract:
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.
Insights
This study reveals how a specific modification in transfer RNAs (tRNAs) regulates essential gene expression in the rice blast fungus. This finding offers a new strategy for developing fungicides to combat fungal pathogens.
Area of Science:
- Molecular Biology
- Mycology
- Biochemistry
Background:
- Ergosterols are vital for fungal cell membranes.
- Controlling ergosterol biosynthesis (ERG) genes is key to managing fungal pathogens like Magnaporthe oryzae.
- Translational control of ERG gene expression is not well understood.
Purpose of the Study:
- To investigate the role of translational mechanisms in regulating ERG gene expression in M. oryzae.
- To identify specific RNA modifications and their impact on fungal virulence.
- To explore novel fungicide development strategies targeting translation and ergosterol pathways.
Main Methods:
- Investigated the Trm6/Trm61 complex's role in catalyzing N1-methyladenosine at position 58 (m1A58) in M. oryzae tRNAs.
- Analyzed the impact of m1A58 on translation initiation and elongation, focusing on eEF1-tRNA binding.
- Assessed the effect of m1A58 absence on ERG gene translation, ergosterol production, and fungal virulence.
- Evaluated the efficacy of simultaneously targeting the Trm6/Trm61 complex and ergosterol biosynthesis for disease control.
Main Results:
- The Trm6/Trm61 complex mediates dynamic m1A58 modification in 51 M. oryzae tRNAs.
- m1A58 enhances translational elongation speed by improving eEF1-tRNA binding.
- Loss of m1A58 significantly reduces ERG gene translation, ergosterol levels, and fungal virulence.
- Combined inhibition of Trm6/Trm61 and ergosterol biosynthesis enhances rice blast control.
Conclusions:
- m1A58-mediated translational regulation is crucial for ergosterol production and M. oryzae infection.
- Targeting tRNA modification and ergosterol biosynthesis presents a promising avenue for novel fungicide development.
- Understanding these translational mechanisms provides insights into fungal pathogenesis and control.
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