4.8 Article

Fungal secondary metabolism is governed by an RNA-binding protein CsdA/RsdA complex

Journal

NATURE COMMUNICATIONS
Volume 14, Issue 1, Pages -

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41467-023-43205-2

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Production of secondary metabolites in eukaryotic cells is regulated by a complex network. Researchers find that the interaction between RNA-binding protein CsdA and regulator RsdA coordinates fungal secondary metabolism. CsdA binds to a specific motif of RsdA's pre-mRNA to control its expression, revealing a mechanism for coordinating fungal secondary metabolism.
Production of secondary metabolites is controlled by a complicated regulatory network in eukaryotic cells. Several layers of regulators are involved in this process, ranging from pathway-specific regulation, to epigenetic control, to global regulation. Here, we discover that interaction of an RNA-binding protein CsdA with a regulator RsdA coordinates fungal secondary metabolism. Employing a genetic deletion approach and transcriptome analysis as well as metabolomics analysis, we reveal that CsdA and RsdA synergistically regulate fungal secondary metabolism comprehensively. Mechanistically, comprehensive genetic and biochemical studies prove that RsdA and CsdA co-localize in the nucleus and physically interact to achieve their functions. In particular, we demonstrate that CsdA mediates rsdA expression by binding specific motif GUCGGUAU of its pre-mRNA at a post-transcriptional level. We thus uncover a mechanism in which RNA-binding protein physically interacts with, and controls the expression level of, the RsdA to coordinate fungal secondary metabolism. RsdA regulates the secondary metabolism in fungi. Here the authors show that RNA-binding protein CsdA interacts with RsdA protein and regulates expression of RsdA, coordinating secondary metabolism in fungi.

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