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Species-specific circular RNA circDS-1 enhances adaptive evolution in Talaromyces marneffei through regulation of dimorphic transition

Summary

Researchers discovered a special type of RNA called circDS-1 that helps a deadly fungus switch between two different forms depending on temperature. This fungus normally grows as a mold in soil but transforms into a yeast when it infects humans at body temperature. The circDS-1 RNA acts like a molecular switch that controls this transformation and helps the fungus cause infection. This discovery reveals that fungi may use hidden genetic elements beyond traditional genes to adapt to their environment.

Background

Thermally dimorphic fungi switch between mold-like mycelia and yeast-like forms in response to temperature changes, which is critical for pathogenicity. While protein-coding genes have been studied extensively, the role of non-coding elements like circular RNAs (circRNAs) in thermal adaptation remains largely unexplored. Talaromyces marneffei serves as an ideal model organism for understanding circRNA roles in fungal thermal adaptation.

Objective

To systematically identify and characterize full-length circRNAs in T. marneffei under mycelial and yeast conditions, and to determine the functional role of circRNAs in dimorphic transition and virulence.

Results

A total of 3,891 high-quality circRNAs were identified, with circDS-1 being the first functional fungal circRNA. CircDS-1 independently promotes hyphae-to-yeast transition, maintains yeast morphology, and regulates virulence. The generation of circDS-1 is driven by a T. marneffei-specific region in the flanking intron that introduces KH-type RNA-binding protein binding motifs.

Conclusion

CircRNAs play important roles in fungal thermal adaptation and pathogenicity, with circDS-1 demonstrating that intronic mutations can drive the generation of functional circRNAs. This reveals a novel molecular mechanism for adaptive evolution beyond protein-coding changes, suggesting that non-coding RNA regulation may be critical for fungal adaptation to host environments.
  • Published in:PLoS Genetics,
  • Study Type:Experimental/Molecular Biology Study,
  • Source: PMID: 40048447, DOI: 10.1371/journal.pgen.1011482
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