The RNA-binding protein Psc1 functions downstream of the NDR/LATS kinase Cbk1 to modulate CO 2 tolerance in Cryptococcus neoformans

Emma E Blackburn; Laura C Ristow; Xiaofeng Xie; Damian J Krysan; Xiaorong Lin

doi:10.1128/mbio.02051-26

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The RNA-binding protein Psc1 functions downstream of the NDR/LATS kinase Cbk1 to modulate CO 2 tolerance in Cryptococcus neoformans

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The RNA-binding protein Psc1 functions downstream of the NDR/LATS kinase Cbk1 to modulate CO 2 tolerance in Cryptococcus neoformans

Emma E Blackburn, Laura C Ristow, Xiaofeng Xie, Damian J Krysan and Xiaorong Lin

mBio, e0205126

09/21/2026

DOI: 10.1128/mbio.02051-26

PMID: 42765704

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Abstract

Cryptococcus neoformans is an opportunistic fungal pathogen responsible for approximately 20% of deaths in patients with HIV/AIDS. Adaptation to host physiological conditions, including high CO2, 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 cbk1Δ and partially rescues its growth defect in high CO2. Psc1 contains multiple consensus cell wall biosynthesis kinase 1 (Cbk1) phosphorylation sites that are required for maintenance of CO2 fitness. We hypothesized that, in the absence of Cbk1, Psc1 negatively regulates CO2 tolerance by binding to and interfering with the function of mRNAs required for CO2 tolerance. Supporting this model, we found that multiple mRNAs that are required for CO2 tolerance associate with Psc1 in the absence of Cbk1. Furthermore, the transcripts of ZDS3, a gene required for CO2 tolerance, predominantly colocalize with Psc1, which forms condensates in the cbk1Δ mutant at high CO2, correlating with impaired growth. Collectively, our findings support the conclusion that C. neoformans adapts to high CO2 through a post-transcriptional mechanism where Cbk1 phosphorylates Psc1, preventing its binding to, and subsequent functional inhibition of, mRNAs important for CO2 tolerance.

stress adaptation

Cryptococcus neoformans

asymmetric localization

virulence

post-transcriptional regulation

biomolecular condensates

Details

Title: Subtitle: The RNA-binding protein Psc1 functions downstream of the NDR/LATS kinase Cbk1 to modulate CO 2 tolerance in Cryptococcus neoformans
Creators: Emma E Blackburn - University of Georgia
Laura C Ristow - University of Iowa
Xiaofeng Xie - University of Georgia
Damian J Krysan - University of Iowa
Xiaorong Lin - University of Georgia
Resource Type: Journal article
Publication Details: mBio, e0205126
DOI: 10.1128/mbio.02051-26
PMID: 42765704
NLM abbreviation: mBio
ISSN: 2150-7511
eISSN: 2150-7511
Publisher: American Society for Microbiology
Grant note: National Institute of Allergy and Infectious Diseases: R01AI147541 University of Georgia: Gene E. Michaels fund
This work was supported by the National Institutes of Health (R01AI147541 to X.L. and D.J.K.) and the University of Georgia Gene E. Michaels Fund (X.L.). The funders had no role in study design, data collection, interpretation, or the decision to submit the work for publication.
Language: English
Electronic publication date: 09/21/2026
Academic Unit: Molecular Physiology and Biophysics; Stead Family Department of Pediatrics; Infectious Disease (Pediatrics)
Record Identifier: 9985236415502771

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