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

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 and Huiquan Liu ()
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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

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-48336-8

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