What is it about?
Think of your genes as a master cookbook (DNA). To cook a meal, you first make a copy of a single recipe (called mRNA). Sometimes, cells need to make a last-minute change to this recipe copy before the dish is made. This process is called RNA editing. In animals, we know which enzymes make these edits, but how fungi did it was a mystery, as they lack the same tools. Our research uncovers the secret machinery fungi use for RNA editing. We found that fungi repurpose a standard cellular enzyme, one that normally works on a different type of RNA (tRNA), to edit their mRNA recipes. The trick is a helper protein we named Ame1. Ame1 acts like a key, activating the enzyme only during the fungus's sexual reproduction phase. This partnership allows the fungus to precisely edit its genetic messages at a crucial stage in its life cycle, revealing a completely new strategy for controlling genetic information.
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Why is it important?
Our work is unique because it solves a long-standing puzzle in biology by identifying the first known mechanism for A-to-I mRNA editing in the fungal kingdom. It reveals a fascinating evolutionary innovation: instead of evolving a new enzyme from scratch, fungi simply recruited a new protein partner (Ame1) to give an old enzyme (Tad2-Tad3) a powerful new function. This discovery is incredibly timely. The field of gene editing is rapidly advancing, and tools that can precisely edit RNA are in high demand for developing new therapies and improving crops. The fungal system we discovered is a brand-new, highly efficient RNA base editor. We've shown it works not only in fungi but also in bacteria, yeast, and even human cells. Because it targets a specific genetic sequence often found in nonsense mutations—a common cause of inherited diseases—it holds immense potential as a new tool for therapeutic and agricultural biotechnology. Furthermore, since this editing process is essential for the spread of major plant pathogens like Fusarium graminearum, our findings open the door to novel, targeted strategies for controlling devastating crop diseases.
Perspectives
When we started this project, the question of how fungi edit their mRNA was a complete black box. The most exciting moment for me was realizing that the answer wasn't a new, undiscovered enzyme, but rather an elegant partnership between two proteins. Discovering that Ame1 was the switch that repurposed a fundamental tRNA-modifying enzyme for a completely different task was a true "aha!" moment. It's a beautiful example of how evolution can work in clever and economical ways. I am particularly proud that our fundamental research has immediate practical implications. Seeing our fungal editing complex successfully work in human cells was a turning point, transforming a fascinating piece of fungal biology into a potential tool that could one day correct disease-causing mutations. It's a powerful reminder that exploring the basic biological diversity of life on Earth can lead to unexpected and transformative technologies that benefit us all. I believe our work not only deepens our understanding of RNA editing but also contributes a valuable new instrument to the genetic editing toolbox.
Prof. Huiquan Liu
Northwest Agriculture and Forestry University
Read the Original
This page is a summary of: Unveiling the A-to-I mRNA editing machinery and its regulation and evolution in fungi, Nature Communications, May 2024, Springer Science + Business Media,
DOI: 10.1038/s41467-024-48336-8.
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