Splicing Fungal Genes Help Cells Change Shape

The opportunistic pathogen Candida albicans grows in two forms: yeast and filament. The latter state contributes to the severity of infections, and elevated temperature promotes this morphological switch. However, the mechanisms that drive this transition are poorly understood.

In a study published in mBio, a research team identified alternative splicing—the selective inclusion or excision of introns in a gene—as a contributor to filament formation in fever-like temperatures.1 Elucidating these pathways could offer novel strategies to target fungi during disease.

The team cultured a collection of mutants at 39 degrees Celsius and used microscopy to identify genes important to filamentation. They found that strains lacking genes relating to mRNA splicing failed to undergo this transition. Alternative splicing promotes adaptation to environmental changes; in fungi, the most common example of alternative splicing is intron retention.

To explore the relationship between splicing and filamentation, the researchers performed RNA sequencing on wild type C. albicans grown at 30 or 39°C. They noted that filamentous fungi induced by higher temperatures retained more introns. They also observed that intron retention decreased gene expression.

The researchers investigated the effect of a splicing mutant on intron retention and gene expression. They observed that while elevated temperatures increased intron retention in wild type cells, the mutant strain retained more introns in genes. However, unlike in wild type cells, splicing mutants with more retained introns lost their gene regulatory ability.

“Understanding why this is the case, understanding how these fluctuations in temperature are sensed and how those signals are transduced into sort of spliceosome function is certainly something that's interesting,” said Nicole Robbins, a mycologist and study author at the University of Toronto.

“[The study] really added to this growing body of evidence that we have a very complex system of different layers of regulation which enable Candida albicans to react in a plastic or adaptable way to its environment,” said Sascha Brunke, a fungal microbiologist at the Leibniz Institute for Natural Product Research and Infection Biology.

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