Fungi Deploy RNA Editing to Rewire Antiviral Defenses, Japanese Scientists Discover.

A team of researchers from Japan has uncovered a sophisticated antiviral defense mechanism in fungi that relies on RNA editing to modulate gene expression and control symptoms during viral infection. The study, conducted using the model fungus Neurospora crassa, highlights how fungi utilize RNA editing, RNA interference (RNAi), and transcriptional regulation to fight off viruses while maintaining cellular health.

The research was led by Associate Professor Shinji Honda of the University of Fukui and Professor Nobuhiro Suzuki of Okayama University, and the results were published in the journal Cell Host & Microbe. Their investigation sheds light on the little-understood mechanisms fungi employ to differentiate between symptomatic and asymptomatic viral infections.

Fungi defend themselves against viral pathogens through three known mechanisms: RNAi, which halts viral replication at the RNA level; transcriptional reprogramming; and the recognition of self versus non-self, which prevents the spread of viruses between fungal cells. Despite many fungal viruses (mycoviruses) being harmless and symptomless in their hosts, the genetic basis for whether or not symptoms appear has remained largely unexplored—until now.

The researchers focused on Neurospora crassa fusarivirus 1 (NcFV1), a mycovirus typically causing no symptoms in wild-type N. crassa. However, the absence of an RNAi system led to severe growth defects and elevated viral RNA levels, suggesting a deeper genetic mechanism at play.

Through mutational and genetic analyses, the team identified two critical genes, old-1 and old-2, which encode enzymes with deaminase domains responsible for A-to-I RNA editing. These enzymes modify messenger RNA (mRNA) near transcription factor genes located just upstream of their own genomic sites. These adjacent regions, dubbed zao-1 and zao-2, are key to the fungus’s antiviral response.

OLD-1 acts as a broad RNA editor, modifying both zao-1 and zao-2 transcripts, while OLD-2 is selective for zao-2. RNA editing by these enzymes enables translation of full-length proteins with zinc finger domains, which play central roles in transcriptional regulation.

The researchers found that symptom development is closely tied to the presence and editing of zao genes. While wild-type fungi with intact zao-1 and zao-2 remained asymptomatic, mutants lacking zao-1 displayed severe symptoms, likely due to unchecked transcriptional activation. Interestingly, double mutants missing both zao-1 and zao-2 recovered to a healthy, symptom-free state, suggesting that the interplay between these genes is critical to immune balance.

Further analysis revealed that in wild-type strains, ZAO-1 proteins are primarily produced in shorter forms, created by transcription start site switching. These short variants likely act as competitive inhibitors to the full-length ZAO proteins. In mutants lacking RNAi (Δqde-2) or zao-1, RNA editing leads to increased production of the full-length forms, particularly ZAO-2FL, resulting in exaggerated antiviral responses and visible symptoms.

The absence of short ZAO-1 variants removes this natural buffering system, allowing full-length ZAO proteins to dominate transcriptional control and exacerbate the immune reaction. This finely tuned regulatory mechanism underscores the delicate balance fungi maintain to avoid self-damage while defending against viruses.

The team also demonstrated that this RNA editing system, along with its target transcription factors, is evolutionarily conserved across various filamentous fungi, including species of Fusarium and Aspergillus.

“This study uncovered a complex layer of antiviral defense involving RNA editing, RNAi, and transcription start site switching,” said Dr. Honda. “It marks a significant turning point in our understanding of fungal-virus interactions and could pave the way for developing robust fungal strains with enhanced viral resistance.”

The findings not only deepen scientific knowledge of fungal immunity but also suggest novel possibilities for genetic engineering and biotechnology applications in agriculture and medicine.

Source:https://phys.org/news/2025-05-fungi-viruses-rna-rewires-genetic.html

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