A posttranscriptional pathway regulates cell wall mRNA expression in budding yeast

Area of Science:

• Mycology
• Molecular Biology
• Cell Biology

Background:

• The fungal cell wall is crucial for protection, structure, and is a key target for antifungal drugs.
• The cell wall integrity (CWI) pathway, a mitogen-activated protein (MAP) kinase cascade, manages transcriptional responses to cell wall damage.

Purpose of the Study:

• To investigate a novel posttranscriptional regulatory pathway that complements the CWI pathway.
• To understand the role of RNA-binding proteins (RBPs) Mrn1 and Nab6 in fungal cell wall homeostasis and antifungal resistance.

Main Methods:

• Identification of target mRNAs for RBPs Mrn1 and Nab6 using 3' UTR analysis.
• Gene deletion studies (Δnab6, Δmrn1) to assess phenotypic consequences.
• Analysis of gene expression and cellular responses to antifungal compounds.

Main Results:

• Mrn1 and Nab6 specifically bind to 3' UTRs of overlapping sets of cell wall-related mRNAs.
• Nab6 stabilizes target mRNAs, maintaining cell wall gene expression during stress.
• Mrn1 destabilizes target mRNAs, opposing Nab6's function.
• Combined deletion of both pathways leads to hypersensitivity to cell wall-targeting antifungal compounds.

Conclusions:

• A posttranscriptional pathway involving Mrn1 and Nab6 works in parallel to the CWI pathway to regulate fungal cell wall integrity.
• This pathway is essential for cellular resistance to antifungal compounds.
• Targeting this pathway could offer new strategies for antifungal drug development.