Fungal pathogens of the Aspergillus genus pose significant threats to human health and food production. Despite progress in understanding pathogenicity mechanisms, a crucial knowledge gap remains regarding the role of long non-coding RNAs (lncRNAs) in the evolution of fungi into successful pathogens. LncRNAs represent a vital yet often overlooked aspect of fungal biology, particularly in how Aspergillus species withstand stress to endure and thrive under adverse conditions. For instance, in Candida auris, the lncRNA DINOR regulates fungal virulence by modulating stress responses and hyphal growth, suggesting that lncRNAs in Aspergillus may similarly influence pathogenic mechanisms.
In our study, we aimed to unravel the role of lncRNAs in responding to changing conditions using a transcriptome analysis of >1000 samples A. flavus, A. fumigatus, A. nidulans, and A. niger available in public databases. Using two different machine learning algorithms we successfully predicted 4022, 1482, 3098, and 3129 potential lncRNAs for A. flavus, A. fumigatus, A. nidulans, and A. niger, respectively. Comparative analysis revealed that lncRNAs in these species share common characteristics, such as shorter length, lower expression levels, and reduced GC content compared to protein-coding genes. Notably, only A. fumigatus, the main pathogenic species, showed a lower proportion of lncRNAs relative to its genome size and a unique enrichment in subtelomeric regions. This finding suggests that the spatial organization of lncRNAs in A. fumigatus may play a critical role in regulating key processes, such as metabolism, contributing to its success as an opportunistic pathogen. We also identified lncRNAs that exhibited differential expression in response to stress and explored their potential functions by analyzing the nearby protein-coding genes. By employing this cis-regulation strategy, we identified diverse Gene Ontology (GO) terms and the biological functions impacted by lncRNAs across the four Aspergillus species.
In conclusion, our approach to identifying lncRNAs in Aspergillus species offers new insights into fungal pathogenicity and potential strategies to combat infections.