A posttranscriptional pathway regulates cell wall mRNA expression in budding yeast

Stefan Bresson; Vadim Shchepachev; David Tollervey

doi:10.1016/j.celrep.2023.112184

A posttranscriptional pathway regulates cell wall mRNA expression in budding yeast

Stefan Bresson, Vadim Shchepachev, David Tollervey

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

The fungal cell wall provides protection and structure and is an important target for antifungal compounds. A mitogen-activated protein (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 report 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 posttranscriptional pathway that mediates cellular resistance to antifungal compounds.

Original language	English
Article number	112184
Number of pages	28
Journal	Cell Reports
Volume	42
Issue number	3
Early online date	28 Feb 2023
DOIs	https://doi.org/10.1016/j.celrep.2023.112184
Publication status	Published - 28 Mar 2023

Keywords / Materials (for Non-textual outputs)

posttranscriptional gene regulation
saccharomyces cerevisiae
UV-crosslinking
stress response
RNA-binding proteins
genetic
cell wall
antifungal
mRNA stability

Access to Document

10.1016/j.celrep.2023.112184Licence: Creative Commons: Attribution (CC-BY)

TollerveyEtal2023APosttranscriptionalPathwayRegulatesFinal published version, 10.1 MBLicence: Creative Commons: Attribution (CC-BY)

1 Finished
2 Active

RNA processing and degradation
Tollervey, D.
UK-based charities
1/10/21 → 30/09/26
Project: Research
Nuclear RNA processing and surveillance
Tollervey, D.
UK-based charities
1/10/16 → 30/09/26
Project: Research
Core funding for the Wellcome Centre for Cell Biology
Marston, A.
UK-based charities
1/12/21 → 30/11/23
Project: Research

Cite this

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title = "A posttranscriptional pathway regulates cell wall mRNA expression in budding yeast",

abstract = "The fungal cell wall provides protection and structure and is an important target for antifungal compounds. A mitogen-activated protein (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 report 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 posttranscriptional pathway that mediates cellular resistance to antifungal compounds.",

keywords = "posttranscriptional gene regulation, saccharomyces cerevisiae, UV-crosslinking, stress response, RNA-binding proteins, genetic, cell wall, antifungal, mRNA stability",

author = "Stefan Bresson and Vadim Shchepachev and David Tollervey",

note = "Funding Information: We thank Richard Clark, Audrey Coutts, and Angie Fawkes from the Edinburgh Wellcome Clinical Research Facility for sequencing services, as well as Shaun Webb from the WCB bioinformatics core facility for maintaining the servers we used for processing sequencing data. This work was funded by Wellcome Principal Research Fellowships to D.T. ( 109916 and 222516 ), also supporting S.B. and V.S., and core funding for the Wellcome Center for Cell Biology ( 203149 ). Publisher Copyright: {\textcopyright} 2023 The Authors",

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AU - Bresson, Stefan

AU - Shchepachev, Vadim

AU - Tollervey, David

N1 - Funding Information: We thank Richard Clark, Audrey Coutts, and Angie Fawkes from the Edinburgh Wellcome Clinical Research Facility for sequencing services, as well as Shaun Webb from the WCB bioinformatics core facility for maintaining the servers we used for processing sequencing data. This work was funded by Wellcome Principal Research Fellowships to D.T. ( 109916 and 222516 ), also supporting S.B. and V.S., and core funding for the Wellcome Center for Cell Biology ( 203149 ). Publisher Copyright: © 2023 The Authors

PY - 2023/3/28

Y1 - 2023/3/28

N2 - The fungal cell wall provides protection and structure and is an important target for antifungal compounds. A mitogen-activated protein (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 report 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 posttranscriptional pathway that mediates cellular resistance to antifungal compounds.

AB - The fungal cell wall provides protection and structure and is an important target for antifungal compounds. A mitogen-activated protein (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 report 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 posttranscriptional pathway that mediates cellular resistance to antifungal compounds.

KW - posttranscriptional gene regulation

KW - saccharomyces cerevisiae

KW - UV-crosslinking

KW - stress response

KW - RNA-binding proteins

KW - genetic

KW - cell wall

KW - antifungal

KW - mRNA stability

U2 - 10.1016/j.celrep.2023.112184

DO - 10.1016/j.celrep.2023.112184

M3 - Article

SN - 2211-1247

VL - 42

JO - Cell Reports

JF - Cell Reports

IS - 3

M1 - 112184

ER -

A posttranscriptional pathway regulates cell wall mRNA expression in budding yeast

Abstract / Description of output

Keywords / Materials (for Non-textual outputs)

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Projects

RNA processing and degradation

Nuclear RNA processing and surveillance

Core funding for the Wellcome Centre for Cell Biology

Cite this