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Unveiling the A-to-I mRNA editing machinery and its regulation and evolution in fungi

Author

Listed:
  • Chanjing Feng

    (College of Plant Protection, Northwest A&F University)

  • Kaiyun Xin

    (College of Plant Protection, Northwest A&F University)

  • Yanfei Du

    (College of Plant Protection, Northwest A&F University)

  • Jingwen Zou

    (College of Plant Protection, Northwest A&F University)

  • Xiaoxing Xing

    (College of Plant Protection, Northwest A&F University)

  • Qi Xiu

    (College of Plant Protection, Northwest A&F University)

  • Yijie Zhang

    (College of Plant Protection, Northwest A&F University)

  • Rui Zhang

    (Northwest A&F University)

  • Weiwei Huang

    (Northwest A&F University)

  • Qinhu Wang

    (College of Plant Protection, Northwest A&F University)

  • Cong Jiang

    (College of Plant Protection, Northwest A&F University)

  • Xiaojie Wang

    (College of Plant Protection, Northwest A&F University)

  • Zhensheng Kang

    (College of Plant Protection, Northwest A&F University)

  • Jin-Rong Xu

    (Purdue University)

  • Huiquan Liu

    (College of Plant Protection, Northwest A&F University)

Abstract

A-to-I mRNA editing in animals is mediated by ADARs, but the mechanism underlying sexual stage-specific A-to-I mRNA editing in fungi remains unknown. Here, we show that the eukaryotic tRNA-specific heterodimeric deaminase FgTad2-FgTad3 is responsible for A-to-I mRNA editing in Fusarium graminearum. This editing capacity relies on the interaction between FgTad3 and a sexual stage-specific protein called Ame1. Although Ame1 orthologs are widely distributed in fungi, the interaction originates in Sordariomycetes. We have identified key residues responsible for the FgTad3-Ame1 interaction. The expression and activity of FgTad2-FgTad3 are regulated through alternative promoters, alternative translation initiation, and post-translational modifications. Our study demonstrates that the FgTad2-FgTad3-Ame1 complex can efficiently edit mRNA in yeasts, bacteria, and human cells, with important implications for the development of base editors in therapy and agriculture. Overall, this study uncovers mechanisms, regulation, and evolution of RNA editing in fungi, highlighting the role of protein-protein interactions in modulating deaminase function.

Suggested Citation

  • Chanjing Feng & Kaiyun Xin & Yanfei Du & Jingwen Zou & Xiaoxing Xing & Qi Xiu & Yijie Zhang & Rui Zhang & Weiwei Huang & Qinhu Wang & Cong Jiang & Xiaojie Wang & Zhensheng Kang & Jin-Rong Xu & Huiquan, 2024. "Unveiling the A-to-I mRNA editing machinery and its regulation and evolution in fungi," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48336-8
    DOI: 10.1038/s41467-024-48336-8
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    References listed on IDEAS

    as
    1. Luciano G. Dolce & Aubree A. Zimmer & Laura Tengo & Félix Weis & Mary Anne T. Rubio & Juan D. Alfonzo & Eva Kowalinski, 2022. "Structural basis for sequence-independent substrate selection by eukaryotic wobble base tRNA deaminase ADAT2/3," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    2. Shuqian Zhang & Bo Yuan & Jixin Cao & Liting Song & Jinlong Chen & Jiayi Qiu & Zilong Qiu & Xing-Ming Zhao & Jingqi Chen & Tian-Lin Cheng, 2023. "TadA orthologs enable both cytosine and adenine editing of base editors," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
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