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However, as most infections are still caused by azole-susceptible Aspergillus strains, there is a need to better understand fungal responses to azole antifungals. To this end, we discover that a long noncoding RNA, afu-182, is a major regulator of cyp51-independent sub-minimum inhibitory concentration (MIC) azole response. We observe that the loss of afu-182 leads to increased surface-attached growth and poorer disease outcomes in a murine model of invasive pulmonary aspergillosis upon azole treatment. In contrast, OE of afu-182 significantly reduces fungal burden in animals treated with the azole drug posaconazole. Importantly, afu-182 levels decrease upon azole exposure, and in an azole adaptation experiment, continuous exposure to low-dose azole led to MIC increase in an afu-182-dependent manner. Whole transcriptome analyses revealed that azole drug treatment leads to an increase in transcripts of genes encoding 7-transmembrane domain proteins of the RTA1 family, and these proteins are negatively regulated by afu-182. Two RTA1 family genes have individual and combined effects and are sufficient to increase fungal susceptibility to azole drugs in the wildtype (WT) strain. Taken together, our data show a role of the long noncoding RNA afu-182 in regulating Aspergillus fumigatus response to azole drugs both in vitro and in vivo.<\/jats:p>","DOI":"10.1093\/genetics\/iyag152","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T05:44:23Z","timestamp":1781502263000},"source":"Crossref","is-referenced-by-count":2,"title":["A long noncoding RNA regulates in vitro and in vivo triazole antifungal susceptibility in\n                    <i>Aspergillus fumigatus<\/i>"],"prefix":"10.1093","volume":"233","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-6197-2211","authenticated-orcid":false,"given":"Nava Raj","family":"Poudyal","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Clemson University , Clemson, SC 29634 ,","place":["United States"]},{"name":"Eukaryotic Pathogen Innovation Center, Clemson University , Clemson, SC 29634 ,","place":["United 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