Tur1 regulates alternative TSS usage in Cryptococcus
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ABSTRACT:
PROVIDER: PRJNA994566 | ENA |
REPOSITORIES: ENA
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Project description:Cryptococcus neoformans is a life-threatening basidiomycete fungal pathogen responsible for meningoencephalitis in immunocompromised patients. This yeast can adapt to diverse habitats, efficiently produces virulence factors, and escapes immune surveillance. This implies intricate mechanisms underlying its gene regulation networks, which are yet to be comprehensively understood. Alternative transcription usage regulation has been identified as the major mean for gene expression regulation in metazoans. However, in fungi, its impact remains elusive as its study has thus far been restricted to model yeasts. We here re-analysed transcription start site (TSS)-seq data to define genuine TSS clusters in two species of pathogenic Cryptococcus. We identified two types of TSS clusters associated with specific DNA sequence motifs. Our analysis also revealed that alternative TSS usage regulation in response to environmental cues is widespread in Cryptococcus, altering gene expression and protein targeting. Importantly, we performed a forward genetic screen to identify a unique transcription factor (TF) named Tur1, which regulates aTSS usage genome-wide when cells switch from exponential phase to stationary phase. Tur1 has been previously shown to be essential for virulence in C. neoformans. Accordingly, we demonstrated here that a tur1Δ mutant strain is more sensitive to superoxide stress and phagocytosed more efficiently by macrophages than the Wild-type (WT) strain.
2024-07-03 | PXD045272 | Pride
Project description:Cryptococcus neoformans is a life-threatening basidiomycete fungal pathogen responsible for meningoencephalitis in immunocompromised patients. This yeast can adapt to diverse habitats, efficiently produces virulence factors, and escapes immune surveillance. This implies intricate mechanisms underlying its gene regulation networks, which are yet to be comprehensively understood. Alternative transcription usage regulation has been identified as the major mean formeans of gene expression regulation in metazoans. However, in fungi, its impact remains elusive as its study has thus far been restricted to model yeasts. We Hhere we re-analysed transcription start site (TSS)-seq data to define genuine TSS clusters in two species of pathogenic Cryptococcus. We identified two types of TSS clusters associated with specific DNA sequence motifs. Our analysis also revealed that alternative TSS usage regulation in response to environmental cues is widespread in Cryptococcus, altering gene expression and protein targeting. Importantly, we performed a forward genetic screen to identify a unique transcription factor (TF) named Tur1, which regulates alternative TSS (aTSS) usage genome-wide when cells switch from exponential phase to stationary phase. Tur1 has been previously shown to be essential for virulence in C. neoformans. Accordingly, we demonstrated here that a tur1? mutant strain is more sensitive to superoxide stress and phagocytosed more efficiently by macrophages than the Wild-type (WT) strain.
2023-07-15 | GSE237320 | GEO
Project description:Neuronal activity regulates alternative exon usage
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Project description:KIS counteracts PTBP2 and regulates alternative exon usage in neurons
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Project description:Alternative mRNA isoforms and long noncoding RNAs (lncRNA) make up a large fraction of the transcriptome and play key functions in cell-fate programming. These transcripts often initiate upstream of coding gene promoters from alternative transcription start sites (TSS) where they can regulate gene expression in cis through transcription-coupled chromatin alterations. How, when and where transcription of alternative cis-acting RNAs regulates local gene expression remains poorly understood. Here, we use a high-resolution quantitative approach to study alternative TSS and transcript end site (TES) usage during three different cell fate transitions in yeast: entry into gametogenesis, commitment to meiotic divisions and return to vegetative growth. We propose that an alternative transcriptome of mRNA isoforms and lncRNAs shapes local gene expression during cell fate transitions. Hence, changes in the types and proportions of different RNAs transcribed at a locus are important inputs for gene expression at distinct stages of development.
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Project description:Alternative RNA splicing is an essential and dynamic process in neuronal differentiation and synapse maturation, and dysregulation of this process has been associated with neurodegenerative diseases. Recent studies have revealed the importance of RNA-binding proteins in the regulation of neuronal splicing programs. However, the molecular mechanisms involved in the control of these splicing regulators are still unclear. Here we show that KIS, a kinase upregulated in the developmental brain, imposes a genome-wide alteration in exon usage during neuronal differentiation. KIS contains a protein-recognition domain common to spliceosomal components and phosphorylates PTBP2, counteracting the role of this splicing factor in exon exclusion. At the molecular level, phosphorylation of unstructured domains within PTBP2 causes its dissociation from two co-regulators, Matrin3 and hnRNPM, and hinders the RNA-binding capability of the complex. Furthermore, KIS and PTBP2 display strong and opposing functional interactions in synaptic spine emergence and maturation. Taken together, our data uncover a post-translational control of splicing regulators that link transcriptional and alternative exon usage programs in neuronal development.
2024-04-25 | PXD050320 | Pride
Project description:Eukaryotes have evolved multiple ATP-dependent chromatin remodelers to shape the nucleosome landscape. We recently uncovered an evolutionarily conserved SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeler complex in plants reminiscent of the mammalian BAF subclass, which specifically incorporates the MINUSCULE (MINU) catalytic subunits and the TRIPLE PHD FINGERS (TPF) signature subunits. Here we report experimental evidence that establishes the functional relevance of TPF proteins for the complex activity. Our results show that depletion of TPF triggers similar pleiotropic phenotypes and molecular defects to those found in minu mutants. Moreover, we report the genomic location of MINU2 and TPF proteins as representative members of the plant BAF-like complex and their impact on nucleosome positioning and transcription. These analyses unravel the binding of the complex to thousands of expressed genes where it modulates the position of the +1 nucleosome. These targets tend to produce 5´-shifted transcripts in the tpf and minu mutants pointing to the participation of the complex in alternative transcriptional start site (TSS) usage. Interestingly, there is a remarkable correlation between +1 nucleosome shift and upstream TSS usage suggesting their functional connection. In summary, this study unravels the function of a plant SWI/SNF complex involved in +1 nucleosome positioning and alternative TSS usage.
2022-09-20 | PXD035892 | Pride
Project description:Synonymous codon usage regulates translation initiation
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Project description:This SuperSeries is composed of the following subset Series: GSE30429: Gene Array Analyzer (GAA): Alternative usage of gene arrays to study alternative splicing events (MoGene array) GSE32998: Gene Array Analyzer (GAA): Alternative usage of gene arrays to study alternative splicing events (MoEx array) Refer to individual Series
2011-11-28 | E-GEOD-33183 | biostudies-arrayexpress
Project description:An alternative transcriptome shapes cell fate transitions in yeast (TSS-seq)
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