State Key Laboratory for Crop Stress Resistance and High-Efficiency Production, College of Plant Protection, Northwest A&F University, Yangling, Shaanxi, 712100, China.
College of Life Sciences, Northwest A&F University, Yangling, Shaanxi, 712100, China.
Nat Commun. 2024 May 10;15(1):3934. doi: 10.1038/s41467-024-48336-8.
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.
在动物中，A-to-I mRNA 编辑是由 ADARs 介导的，但真菌中性阶段特异性 A-to-I mRNA 编辑的机制尚不清楚。在这里，我们表明真核 tRNA 特异性异二聚体脱氨酶 FgTad2-FgTad3 负责禾谷镰刀菌中的 A-to-I mRNA 编辑。这种编辑能力依赖于 FgTad3 与一种称为 Ame1 的性阶段特异性蛋白之间的相互作用。尽管 Ame1 同源物在真菌中广泛分布，但这种相互作用起源于 Sordariomycetes。我们已经确定了负责 FgTad3-Ame1 相互作用的关键残基。FgTad2-FgTad3 的表达和活性受不同启动子、不同翻译起始和翻译后修饰的调节。我们的研究表明，FgTad2-FgTad3-Ame1 复合物可以在酵母、细菌和人类细胞中有效编辑 mRNA，这对治疗和农业中碱基编辑器的发展具有重要意义。总的来说，这项研究揭示了真菌中 RNA 编辑的机制、调节和进化，强调了蛋白质-蛋白质相互作用在调节脱氨酶功能中的作用。
