Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Song Z

PROVIDER: S-EPMC10645843 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Song Zili Z Zhou Shuang S Zhang Hongjiao H Keller Nancy P NP Oakley Berl R BR Liu Xiao X Yin Wen-Bing WB

Nature communications 20231114 1

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 ...[more]

PMID: 37963872

Similar Datasets

Project description:RNA-binding protein Nrd1 plays a role in RNA polymerase II transcription termination. In this study, we showed that the orthologous NrdA is important in global mRNA expression and secondary metabolism in Aspergillus species. We constructed an nrdA conditional expression strain using the Tet-On system in Aspergillus luchuenesis mut. kawachii. Downregulation of nrdA caused a severe growth defect, indicating that NrdA is essential for the proliferation of A. kawachii. Parallel RNA-sequencing and RNA immunoprecipitation-sequencing analysis identified potential NrdA-interacting transcripts, corresponding to 32% of the predicted protein-coding genes of A. kawachii. Subsequent gene ontology analysis suggested that overexpression of NrdA affects the production of secondary metabolites. To clarify this, we constructed Aspergillus nidulans, Aspergillus fumigatus, and Aspergillus oryzae strains overexpressing NrdA in the early developmental stage. Overexpression of NrdA reduced the production of sterigmatocystin and penicillin in A. nidulans, as well as that of helvolic acid and pyripyropene A in A. fumigatus. Moreover, it increased the production of kojic acid and reduced the production of penicillin in A. oryzae. These effects were accompanied by almost consistent changes in the mRNA levels of relevant genes. Collectively, these results suggest that NrdA is the essential RNA-binding protein, which plays a significant role in global gene expression and secondary metabolism in Aspergillus species.IMPORTANCENrd1, a component of the Nrd1-Nab3-Sen1 complex, is an essential RNA-binding protein involved in transcriptional termination in yeast. However, its role in filamentous fungi has not been studied. In this study, we characterized an orthologous NrdA in the Aspergillus species, identified potential NrdA-interacting mRNA, and investigated the effect of overexpression of NrdA on mRNA expression in Aspergillus luchuensis mut. kawachii. The results indicated that NrdA controls global gene expression involved in versatile metabolic pathways, including the secondary metabolic process, at least in the early developmental stage. We demonstrated that NrdA overexpression significantly affected the production of secondary metabolites in Aspergillus nidulans, Aspergillus oryzae, and Aspergillus fumigatus. Our findings are of importance to the fungal research community because the secondary metabolism is an industrially and clinically important aspect for the Aspergillus species.

Project description:BackgroundRNA-binding proteins interact with specific RNA molecules to regulate important cellular processes. It is therefore necessary to identify the RNA interaction partners in order to understand the precise functions of such proteins. Protein-RNA interactions are typically characterized using in vivo and in vitro experiments but these may not detect all binding partners. Therefore, computational methods that capture the protein-dependent nature of such binding interactions could help to predict potential binding partners in silico.ResultsWe have developed three methods to predict whether an RNA can interact with a particular RNA-binding protein using support vector machines and different features based on the sequence (the Oli method), the motif score (the OliMo method) and the secondary structure (the OliMoSS method). We applied these approaches to different experimentally-derived datasets and compared the predictions with RNAcontext and RPISeq. Oli outperformed OliMoSS and RPISeq, confirming our protein-specific predictions and suggesting that tetranucleotide frequencies are appropriate discriminative features. Oli and RNAcontext were the most competitive methods in terms of the area under curve. A precision-recall curve analysis achieved higher precision values for Oli. On a second experimental dataset including real negative binding information, Oli outperformed RNAcontext with a precision of 0.73 vs. 0.59.ConclusionsOur experiments showed that features based on primary sequence information are sufficiently discriminating to predict specific RNA-protein interactions. Sequence motifs and secondary structure information were not necessary to improve these predictions. Finally we confirmed that protein-specific experimental data concerning RNA-protein interactions are valuable sources of information that can be used for the efficient training of models for in silico predictions. The scripts are available upon request to the corresponding author.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets