Omics · study · 2026
NMD-mediated control of Tor influences adaptation to nutrient and temperature conditions in Cryptococcus neoformans
Listed in NCBI GEO
The yeast Cryptococcus neoformans is an opportunistic human pathogen capable of surviving within various environmental conditions.
Description
The repertoire of antifungal agents effective in treating cryptococcal infection is limited, necessitating the identification of alternative treatment strategies. Nonsense-mediated decay (NMD) is an RNA decay mechanism that serves as a post-transcriptional regulator of gene expression.
While the absence of NMD in C. neoformans sensitizes cells to the antifungal fluconazole, the mechanism underlying this sensitivity and role of NMD in C. neoformans biology remained unexplored. Using phenotypic analysis and RNA-sequencing analysis, we identify basal dysregulation of thermal- and nutrient-adaptive genes and demonstrate temperature- and/or nutrient-dependent phenotypic suppression of upf1Δ phenotypes, including fluconazole sensitivity and resistance to rapamycin.
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We determine rapamycin co-treatment also suppresses the upf1Δ fluconazole sensitivity, implicating dysregulation of Tor signaling in phenotypic outcomes when NMD is absent. We then investigate Tor-sensitive signaling in the upf1Δ mutant, finding inhibition of cell wall integrity (CWI) signaling and hyperactivation of the kinase Gcn2, both of which returned to wildtype-like levels by either rapamycin treatment, nutrient limitation, or constitutive thermal stress.
These results indicated NMD is required for appropriate regulation of Tor signaling in unstressed conditions and suggested upf1Δ phenotypes are driven in part by Tor hyperactivation. A phenotypic screen of mutants lacking Tor regulators revealed that deletion of the Tor-suppressing IML1 gene recapitulates upf1Δ phenotypes and signaling defects, consistent with Tor hyperactivation. Taken together, our results suggest NMD participates in the regulation of Tor signaling in C. neoformans.
Future work will investigate how specific targets of NMD impact Tor signaling and promote fluconazole sensitivity in C. neoformans.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE319nnn/GSE319882 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE319882 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1425471 ncbi.nlm.nih.gov/bioproject/PRJNA1425471 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing
- From keywords
- Life Sciences
Provenance · 1 source records, 6 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE319882 | 14 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |