Large-scale genome re-annotation uncovers pathogen-specific lncRNA regulators of fungal growth and virulence
- 1Jiangsu Key Laboratory for Pathogens and Ecosystems, Jiangsu Engineering and Technology Research Centre for Microbiology, College of Life Sciences, Nanjing Normal University, Nanjing, China
- 2Department of Respiratory and Critical Care, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, China
- 3Department of Respiratory and Critical Care, Shandong Second Medical University, Weifang, China
Abstract
Invasive fungal infections pose a serious global health threat. Although core cellular processes are broadly conserved across fungi, only a small fraction of known species cause severe human disease, suggesting that pathogenicity may depend in part on pathogen-specific regulators. However, such elements remain poorly understood because they often lack recognizable homologs, limiting accurate annotation and functional characterization. Here, using the invasive mold Aspergillus fumigatus as a model, we combined transcriptome-guided re-annotation with functional screening to identify previously unrecognized long non-coding RNAs (lncRNAs) required for fungal growth and virulence. Among 423 loci previously annotated as Fumigati section-specific protein-coding genes, 176 were reclassified as non-coding, revealing widespread annotation errors that had obscured potential regulators. We identified two lncRNAs, SSP7 and SSP8, that are required for hyphal growth and virulence in a murine infection model. Mechanistically, SSP7 binds the coding region of pprA mRNA, promotes its association with polysomes and translation, and thereby sustains mitochondrial function, whereas SSP8 contributes to amino acid homeostasis. Together, these findings demonstrate for the first time that pathogen-specific lncRNAs can fine-tune conserved cellular processes to generate distinct fungal growth and virulence traits, and reveal a novel translational regulatory mechanism in fungal pathogenicity. Author summary: Fungal infections are a major threat to human health, yet only a small fraction of fungal species can cause severe disease. We asked whether genetic elements found only in particular groups of pathogenic fungi might contribute to these differences. Using the major human fungal pathogen Aspergillus fumigatus as a model, we re-annotated a set of genes previously annotated as protein-coding and found that many had been misannotated. Instead, a large proportion produce long non-coding RNAs (lncRNAs), which do not encode proteins but can regulate cellular functions. We identified two such lncRNAs, SSP7 and SSP8, that are important for fungal growth and virulence. SSP7 helps maintain translation of a conserved protein required for mitochondrial function, whereas SSP8 contributes to maintaining balanced amino acid levels. Together, these results suggest that fungal-specific non-coding RNAs can influence fundamental cellular processes and pathogenicity. They also highlight the importance of accurate genome annotation for uncovering previously overlooked regulators in fungal pathogens.
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BibTeX
@article{gao2026largescale,
title = {{Large-scale genome re-annotation uncovers pathogen-specific lncRNA regulators of fungal growth and virulence}},
author = {Renwei Gao and Zhenxiu Liu and Han Tang and Ning Wang and Xinying Xue and Ling Lu and Yuanwei Zhang},
journal = {PLOS Pathogens},
year = {2026},
month = oct,
doi = {10.1371/journal.ppat.1014681},
url = {https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014681},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Large-scale genome re-annotation uncovers pathogen-specific lncRNA regulators of fungal growth and virulence
AU - Renwei Gao
AU - Zhenxiu Liu
AU - Han Tang
AU - Ning Wang
AU - Xinying Xue
AU - Ling Lu
AU - Yuanwei Zhang
PY - 2026
DA - 2026/10/09
JO - PLOS Pathogens
DO - 10.1371/journal.ppat.1014681
UR - https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014681
AB - Invasive fungal infections pose a serious global health threat. Although core cellular processes are broadly conserved across fungi, only a small fraction of known species cause severe human disease, suggesting that pathogenicity may depend in part on pathogen-specific regulators. However, such elements remain poorly understood because they often lack recognizable homologs, limiting accurate annotation and functional characterization. Here, using the invasive mold Aspergillus fumigatus as a model, we combined transcriptome-guided re-annotation with functional screening to identify previously unrecognized long non-coding RNAs (lncRNAs) required for fungal growth and virulence. Among 423 loci previously annotated as Fumigati section-specific protein-coding genes, 176 were reclassified as non-coding, revealing widespread annotation errors that had obscured potential regulators. We identified two lncRNAs, SSP7 and SSP8, that are required for hyphal growth and virulence in a murine infection model. Mechanistically, SSP7 binds the coding region of pprA mRNA, promotes its association with polysomes and translation, and thereby sustains mitochondrial function, whereas SSP8 contributes to amino acid homeostasis. Together, these findings demonstrate for the first time that pathogen-specific lncRNAs can fine-tune conserved cellular processes to generate distinct fungal growth and virulence traits, and reveal a novel translational regulatory mechanism in fungal pathogenicity. Author summary: Fungal infections are a major threat to human health, yet only a small fraction of fungal species can cause severe disease. We asked whether genetic elements found only in particular groups of pathogenic fungi might contribute to these differences. Using the major human fungal pathogen Aspergillus fumigatus as a model, we re-annotated a set of genes previously annotated as protein-coding and found that many had been misannotated. Instead, a large proportion produce long non-coding RNAs (lncRNAs), which do not encode proteins but can regulate cellular functions. We identified two such lncRNAs, SSP7 and SSP8, that are important for fungal growth and virulence. SSP7 helps maintain translation of a conserved protein required for mitochondrial function, whereas SSP8 contributes to maintaining balanced amino acid levels. Together, these results suggest that fungal-specific non-coding RNAs can influence fundamental cellular processes and pathogenicity. They also highlight the importance of accurate genome annotation for uncovering previously overlooked regulators in fungal pathogens.
SN - 1553-7374
ER -