biostudies-literatureYadav VNIAID NIH HHSDuke University Center for AIDS ResearchNIAIDNIHiyae010https://www.ebi.ac.uk/biostudies/studies/S-EPMC10917508biostudies-literatureUnknown226(3)Adaptation to external environmental challenges at the cellular level requires rapid responses and involves relay of information to the nucleus to drive key gene expression changes through downstream transcription factors. Here, we describe an alternative route of adaptation through a direct role for cellular signaling components in governing gene expression via RNA interference-mediated small RNA production. Calcium-calcineurin signaling is a highly conserved signaling cascade that plays central roles in stress adaptation and virulence of eukaryotic pathogens, including the human fungal pathogen Cryptococcus neoformans. Upon activation in C. neoformans, calcineurin localizes to P-bodies, membraneless organelles that are also the site for RNA processing. Here, we studied the role of calcinGeneticsCalcineurin contributes to RNAi-mediated transgene silencing and small interfering RNA production in the human fungal pathogen Cryptococcus neoformans.PMC10917508AI170543-02AI039115-26P30 AI064518AI33654-06R01 AI170543AI050113-19R01 AI039115R01 AI050113Mohan RSun SYadav VHeitman JfalseCalcineurin contributes to RNAi-mediated transgene silencing and small interfering RNA production in the human fungal pathogen Cryptococcus neoformans.Adaptation to external environmental challenges at the cellular level requires rapid responses and involves relay of information to the nucleus to drive key gene expression changes through downstream transcription factors. Here, we describe an alternative route of adaptation through a direct role for cellular signaling components in governing gene expression via RNA interference-mediated small RNA production. Calcium-calcineurin signaling is a highly conserved signaling cascade that plays central roles in stress adaptation and virulence of eukaryotic pathogens, including the human fungal pathogen Cryptococcus neoformans. Upon activation in C. neoformans, calcineurin localizes to P-bodies, membraneless organelles that are also the site for RNA processing. Here, we studied the role of calcin2024-01-01T00:00:00Z2024 Mar2026-07-15T05:01:31.195Z2025-04-04T00:08:44.537ZS-EPMC109175083827993710.1093/genetics/iyae010