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Posttranscriptional regulation of cell wall integrity in budding yeast
Open accessPreprint — published as 10.1016/j.celrep.2023.112184 · Paper page
Abstract
The fungal cell wall provides protection and structure, and is an important target for antifungal compounds. A MAP kinase cascade termed the cell wall integrity (CWI) pathway regulates transcriptional responses to cell wall damage. Here we describe a posttranscriptional pathway that plays an important complementary role. We discovered that the RNA-binding proteins (RBPs) Mrn1 and Nab6 specifically target the 3’ UTRs of a largely overlapping set of cell wall-related mRNAs. These mRNAs are downregulated in the absence of Nab6, indicating a function in target mRNA stabilization. Nab6 acts in parallel to CWI signaling to maintain appropriate expression of cell wall genes during stress. Cells lacking both pathways are hypersensitive to antifungal compounds targeting the cell wall. Deletion of MRN1 partially alleviates growth defects associated with Δnab6 and Mrn1 has an opposing function in mRNA destabilization. Our results uncover a novel posttranscriptional pathway which mediates cellular resistance to antifungal compounds.
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Highly accurate protein structure prediction with AlphaFold
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Metadata
- Authors
- Bresson, S., Shchepachev, V., & Tollervey, D.
- Affiliations
- Wellcome Centre for Cell Biology (GB)
- Corresponding author
- Bresson, Stefan
- Tollervey, David
- Venue
- Cell Reports
- Publisher
- openRxiv
- Published
- 2022-10-01
- Volume
- 42
- Issue
- 3
- Pages
- 112184-112184
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W4322603888
- Cited by
- 10
- References
- 1
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 3 · 2023: 1
- FWCI
- 0.89
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Cell Reports (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
- Funders
- Wellcome Trust (222516/Z/21/Z, 109916/Z/15/Z)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Keywords
- cell wall integrity pathway, post-transcriptional regulation, RNA-binding proteins, 3' untranslated region, mRNA stability, mRNA destabilization, antifungal resistance, cell wall stress, Saccharomyces cerevisiae, MAPK signaling
- MeSH terms
- Antifungal Agents, Cell Wall, Saccharomycetales, RNA, Messenger, Saccharomyces cerevisiae, Gene Expression Regulation, Fungal, Saccharomyces cerevisiae Proteins
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