Beyond gene duplication: A-to-I RNA editing-mediated stop codon readthrough modulates Dbf2 dosage to resolve...

Area of Science:

• Molecular Biology
• Mycology
• Genetics

Background:

• Stop codon readthrough is often considered translational noise but occurs specifically in certain tissues and stages, suggesting adaptive roles in proteome tuning.
• Organisms face trade-offs between different life stages, such as growth and reproduction, which can be mitigated without genomic changes.

Purpose of the Study:

• To investigate if RNA editing mechanisms can resolve stage-specific trade-offs without altering the genome.
• To understand the role of "stop-loss" RNA editing in the filamentous ascomycete Fusarium graminearum, specifically in the NDR kinase gene FgDBF2.

Main Methods:

• Developmental genetic and cell biological analyses in Fusarium graminearum.
• Investigating the effects of blocking RNA editing and altering FgDBF2 dosage.
• Comparative and transcriptomic analyses across Sordariomycetes.

Main Results:

• Fusarium graminearum utilizes developmentally programmed A-to-I RNA editing of FgDBF2 (UAG to UIG) instead of readthrough.
• This editing creates a destabilizing C-terminal extension, reducing FgDbf2 levels during ascospore formation and promoting accurate spore encapsulation.
• Blocking editing or increasing unedited FgDbf2 leads to malformed spores, while constitutive editing impairs vegetative growth, indicating dosage sensitivity and stage-specific antagonism.

Conclusions:

• Stage-specific stop-loss RNA editing is a mechanism to buffer dosage, transiently reducing NDR kinase abundance during ascospore formation.
• This process alleviates growth-reproduction trade-offs without requiring gene duplication.
• Conservation of stop-loss editing in Sordariomycetes suggests a widespread adaptive strategy for proteome regulation.