A long non-coding RNA, <i>afu-254</i> , is required for the oxidative stress response, cell wall stress response, azole susceptibility and virulence in <i>Aspergillus fumigatus</i>

Long non-coding RNAs play an important role in stress response in all forms of life; however, a tight regulation of lncRNAs is required for normal function. Abnormal expression of lncRNA is associated with uncontrolled cell growth in many forms of cancer. Recent studies have highlighted the role of lncRNAs in <i>Aspergillus fumigatus</i> in azole stress response and virulence. Here, using a transcriptome dataset of <i>A. fumigatus</i> response to stress, we identified <i>afu-254</i> as an 854bp lncRNA that plays a role in modulating oxidative stress, fungal sub-MIC azole response to posaconazole and itraconazole, cell wall stress, macrophage phagocytosis and killing <i>ex vivo</i>, and virulence in an invertebrate model of <i>Aspergillus</i> infection. Importantly, <i>afu-254</i> does not produce cross-azole susceptible response and plays a role in fungal azole response against posaconazole and itraconazole but not voriconazole. Furthermore, we showed that stochiometric levels of <i>afu-254</i> are important for its function, and ectopic overexpression of <i>afu-254</i> in the WT strain leads to an antimorph. This phenotype may stem from a higher ordered structure that is denatured with heat, indicating the presence of a non-functional isoform. In conclusion, we characterized a novel lncRNA, <i>afu-254</i>, that is important for stress response and virulence in the pathogenic fungus <i>A. fumigatus</i>.