{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T19:38:51Z","timestamp":1793129931430,"version":"4.5.0"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI147541"],"award-info":[{"award-number":["R01AI147541"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007699","name":"University of Georgia","doi-asserted-by":"publisher","award":["Gene E. Michaels fund"],"award-info":[{"award-number":["Gene E. Michaels fund"]}],"id":[{"id":"10.13039\/100007699","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2026,10,14]]},"abstract":"ABSTRACT<\/jats:title>\n \n \n \n Cryptococcus neoformans<\/jats:italic>\n is an opportunistic fungal pathogen responsible for approximately 20% of deaths in patients with HIV\/AIDS. Adaptation to host physiological conditions, including high CO\n 2<\/jats:sub>\n , is required for infection. We discovered that an uncharacterized protein with an RNA-binding domain, Psc1, functions as a basidiomycete-specific suppressor of the kinase mutant\n cbk1<\/jats:italic>\n \u0394 and partially rescues its growth defect in high CO\n 2<\/jats:sub>\n . Psc1 contains multiple consensus\n c<\/jats:underline>\n ell wall\n b<\/jats:underline>\n iosynthesis\n k<\/jats:underline>\n inase 1 (Cbk1) phosphorylation sites that are required for maintenance of CO\n 2<\/jats:sub>\n fitness. We hypothesized that, in the absence of Cbk1, Psc1 negatively regulates CO\n 2<\/jats:sub>\n tolerance by binding to and interfering with the function of mRNAs required for CO\n 2<\/jats:sub>\n tolerance. Supporting this model, we found that multiple mRNAs that are required for CO\n 2<\/jats:sub>\n tolerance associate with Psc1 in the absence of Cbk1. Furthermore, the transcripts of\n ZDS3<\/jats:italic>\n , a gene required for CO\n 2<\/jats:sub>\n tolerance, predominantly colocalize with Psc1, which forms condensates in the\n cbk1<\/jats:italic>\n \u0394 mutant at high CO\n 2<\/jats:sub>\n , correlating with impaired growth. Collectively, our findings support the conclusion that\n C. neoformans<\/jats:italic>\n adapts to high CO\n 2<\/jats:sub>\n through a post-transcriptional mechanism where Cbk1 phosphorylates Psc1, preventing its binding to, and subsequent functional inhibition of, mRNAs important for CO\n 2<\/jats:sub>\n tolerance.\n <\/jats:p>\n \n IMPORTANCE<\/jats:title>\n \n High CO\n 2<\/jats:sub>\n is growth-inhibitory, and therefore adaptation to high CO\n 2<\/jats:sub>\n stress is a universal cellular phenomenon required for survival. The environmental fungus,\n Cryptococcus neoformans<\/jats:italic>\n , encounters high CO\n 2<\/jats:sub>\n environments in the host, and thus tolerance to high CO\n 2<\/jats:sub>\n is critical for its ability to cause lethal infections. The regulation of\n A<\/jats:underline>\n ce2p and morphogenesis (RAM) pathway is required for its growth in high CO\n 2<\/jats:sub>\n . We found that CO\n 2<\/jats:sub>\n tolerance is mediated post-transcriptionally by a downstream target of the RAM pathway, the RNA-binding protein Psc1. In the absence of the RAM pathway, Psc1 sequesters mRNA transcripts required for growth in high CO\n 2<\/jats:sub>\n , preventing growth. These findings reveal a previously uncharacterized post-transcriptional regulatory mechanism that controls cryptococcal adaptation to high CO\n 2<\/jats:sub>\n .\n <\/jats:p>\n <\/jats:sec>\n <\/jats:sec>","DOI":"10.1128\/mbio.02051-26","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T13:01:31Z","timestamp":1789995691000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["The RNA-binding protein Psc1 functions downstream of the NDR\/LATS kinase Cbk1 to modulate CO\n 2<\/sub>\n tolerance in\n Cryptococcus neoformans<\/i>"],"prefix":"10.1128","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-2218-0257","authenticated-orcid":true,"given":"Emma E.","family":"Blackburn","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02bjhwk41","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology, University of Georgia","place":["Athens, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura C.","family":"Ristow","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036jqmy94","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pediatrics, Carver College of Medicine, University of Iowa","place":["Iowa City, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Xie","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02bjhwk41","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology, University of Georgia","place":["Athens, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6330-3365","authenticated-orcid":true,"given":"Damian J.","family":"Krysan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036jqmy94","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pediatrics, Carver 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