Research

Our research aims to understand the molecular mechanisms governing mRNA biogenesis, with particular emphasis on the coordination of RNA processing, messenger ribonucleoprotein (mRNP) assembly and nuclear export. By combining mechanistic studies with cellular approaches, we investigate how these essential processes regulate gene expression and explore their potential as targets for antifungal intervention.

Molecular mechanisms of mRNA processing, mRNP assembly and nuclear export

The production of functional messenger RNA (mRNA) requires the coordinated activities of transcription, RNA processing and mRNP assembly. During transcription, nascent mRNAs undergo processing steps such as capping, splicing and 3′-end cleavage and polyadenylation, while associating with RNA-binding proteins to form mRNPs. The interplay between these processes determines how mRNAs are matured, quality-controlled and exported to the cytoplasm for translation.

Our research seeks to uncover the molecular mechanisms that coordinate these events and ensure the production of functional mRNPs. We are particularly interested in how mRNA 3′-end formation is coupled to mRNP assembly, how poly(A) tail length is controlled, and how mRNP maturation influences nuclear export and quality control.

To address these questions, we combine biochemical reconstitution, quantitative kinetic and biophysical analyses, and structural approaches with molecular and cellular studies in the budding yeast Saccharomyces cerevisiae. By reconstructing RNA-processing reactions from purified components and examining their regulation in living cells, we aim to establish how molecular interactions and dynamic regulatory mechanisms govern mRNA biogenesis.

Targeting fungal mRNA biogenesis for antifungal intervention

Invasive fungal infections pose a significant global health challenge, particularly among immunocompromised patients. With limited treatment options and increasing antifungal resistance, there is an urgent need to identify new therapeutic targets and compounds with novel mechanisms of action.

Although the core machinery of gene expression is conserved across eukaryotes, differences in the molecular mechanisms and regulation of RNA processing between fungi and humans may provide opportunities for selective inhibition. Our research investigates these differences to identify vulnerabilities in essential fungal gene expression pathways, with particular emphasis on mRNA 3′-end formation and polyadenylation.

Using the human fungal pathogen Candida albicans as a principal model, we combine biochemical and structural studies of RNA-processing machinery with fungal molecular biology and cellular approaches. We investigate how small-molecule inhibitors interfere with essential RNA-processing reactions, how these effects influence fungal gene expression and physiology, and which molecular features determine their selectivity between fungal and human systems.

Our long-term goal is to establish the molecular basis for targeting fungal mRNA biogenesis and contribute to the development of antifungal therapies with novel mechanisms of action.

 

mRNA 3′-end processing pathways differ between yeast (A) and mammals (B). Image from Rodríguez-Molina & Turtola (2023).