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Xrp1 governs the stress response program to spliceosome dysfunction

ABSTRACT: Xrp1 governs the stress response program to spliceosome dysfunction

PROVIDER: PRJNA880351 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR21554781_1.fastq.gz	Fastqsanger.gz
	SRR21554781_2.fastq.gz	Fastqsanger.gz
	SRR21554782_1.fastq.gz	Fastqsanger.gz
	SRR21554782_2.fastq.gz	Fastqsanger.gz
	SRR21554783_1.fastq.gz	Fastqsanger.gz

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Xrp1 governs the stress response program to spliceosome dysfunction

Project description:Xrp1 governs the stress response program to spliceosome dysfunction

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Xrp1 governs the stress response program to spliceosome dysfunction

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Xrp1 governs the stress response program to spliceosome dysfunction

Project description:We investigated the changes in gene expression in response to reduced levels of Ecdysoneless (Ecd), and the role of Xrp1 in induction of transcriptional changes upon loss of Ecd in the developing wing disc of Drosophila. To do this we utilized the GAL4/UAS system to express UAS-ecd-RNAi alone and in combination with UAS-xrp1-RNAi in the nubbin-domain (nub-Gal4, UAS-mRFP, UAS-ecd-RNAi and nub-Gal4, UAS-mRFP, UAS-ecd-RNAi, xrp1-RNAi) of the wing disc and used nub-Gal4, UAS-mRFP wing discs as controls. We quantified transcriptomic expression analysis from four biological replicates for both experimental groups

2024-01-31 | GSE213298 | GEO

Xrp1 governs the stress response program to spliceosome dysfunction.

Project description:Co-transcriptional processing of nascent pre-mRNAs by the spliceosome is vital to regulating gene expression and maintaining genome integrity. Here, we show that the deficiency of functional U5 small nuclear ribonucleoprotein particles (snRNPs) in Drosophila imaginal cells causes extensive transcriptome remodeling and accumulation of highly mutagenic R-loops, triggering a robust stress response and cell cycle arrest. Despite compromised proliferative capacity, the U5 snRNP-deficient cells increased protein translation and cell size, causing intra-organ growth disbalance before being gradually eliminated via apoptosis. We identify the Xrp1-Irbp18 heterodimer as the primary driver of transcriptional and cellular stress program downstream of U5 snRNP malfunction. Knockdown of Xrp1 or Irbp18 in U5 snRNP-deficient cells attenuated JNK and p53 activity, restored normal cell cycle progression and growth, and inhibited cell death. Reducing Xrp1-Irbp18, however, did not rescue the splicing defects, highlighting the requirement of accurate splicing for cellular and tissue homeostasis. Our work provides novel insights into the crosstalk between splicing and the DNA damage response and defines the Xrp1-Irbp18 heterodimer as a critical sensor of spliceosome malfunction and mediator of the stress-induced cellular senescence program.

| S-EPMC10954486 | biostudies-literature

Xrp1 governs the stress response program to spliceosome dysfunction

Project description:Unperturbed pre-mRNA splicing is crucial for proper expression of eukaryotic genes, but also maintenance of genome integrity. Loss of splicing factors is associated to DNA damage arising through different mechanisms, among which is the accumulation of mutagenic DNA/RNA hybrids (R-loops). RNase H1 recognizes and degrades the RNA moiety within R-loops, and is a commonly used marker for R-loops. Ecdysoneless protein was previously shown to participate in pre-mRNA splicing through its association with the U5 snRNP. In this study we have performed in vivo Targeted DamID using the Dam-RNase H1 construct to map the localization of R-loops throughout the Drosophila genome in control and Ecd-deficient Drosophila wing imaginal discs.

2024-01-31 | GSE213325 | GEO

Xrp1 governs the stress response program to spliceosome dysfunction

Project description:We investigated the changes in gene expression in response to reduced levels of Ecdysoneless (Ecd) in the developing wing disc of Drosophila. To do this we utilized the GAL4/UAS system to express UAS-ecd-RNAi in the nubbin-domain (nub-Gal4, UAS-mRFP, UAS-ecd-RNAi) of the wing disc and used Nub-Gal4/+ wing discs as controls. We quantified transcriptomic expression analysis from four biological replicates for both experimental groups

2024-01-31 | GSE203127 | GEO

DROSOPHILA FUS MUTANT PHENOTYPES ARE MEDIATED BY INCREASED XRP1 EXPRESSION LEADING TO GENE EXPRESSION DYSREGULATION

Project description:Several RNA-binding proteins (RBPs) are implicated in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), including the FET proteins FUS, TAF15 and EWSR1. Cabeza (caz) is the single Drosophila FET ortholog. Here, we identified Xrp1, a poorly characterized DNA-binding protein, as a key modifier of caz mutant phenotypes. Xrp1 expression was strongly upregulated in caz mutants, and Xrp1 heterozygosity rescued their motor defects and life span. Interestingly, selective neuronal Xrp1 knock-down was sufficient to rescue, and neuronal Xrp1 overexpression phenocopied caz mutant phenotypes. The caz/Xrp1 genetic interaction depended on the functionality of the AT-hook DNA-binding domain in Xrp1. Consistently, caz mutants displayed gene expression dysregulation, which was mitigated by Xrp1 heterozygosity. Finally, Xrp1 knock-down substantially rescued the motor deficits and life span of flies expressing ALS-mutant FUS in motor neurons. Taken together, caz mutant phenotypes are mediated by increased neuronal Xrp1 levels, leading to gene expression dysregulation and neuronal dysfunction.

2018-09-06 | PXD008417 | Pride

RNA-seq analysis to assess transcriptional effects of Rp mutations in wing imaginal discs and their dependence on Xrp1

Project description:Since the putative transcription factor Xrp1 gene is required for many aspects of Rp+/- phenotypes, we sought to define what transcriptional changes occur in Rp+/- wing discs and their dependence on Xrp1. We identified 257 genes whose transcripts were significantly altered in the same direction in two Rp+/- genotypes, most of which depended on Xrp1. The results show that Xrp1 regulates a significant transcriptional response in Rp+/- genotypes.

2018-08-20 | GSE112864 | GEO

Single-cell level gene expression profiles of enteroendocrine cell lineages, control guts and guts with Xrp1 overexpressed in EEs

Project description:Differentiated cells exhibit cell plasticity, where they dedifferentiate to stem cells or trans-differentiate into cells of another lineage, when necessary. We studied the cell plasticity of secretory enternendocrine cells (EEs) in the fruit fly Drosophila melanogaster. We resolved single-cell transcriptomics of EEs and cells derived from EEs. Our scRNA-seq data of EE lineages have characterized intermediate cell types derived from EEs. We also specifically focused on a gene called Xrp1 and examined potential changes of all epithelial cell types by EE-specific Xrp1 overexpression (O/E). Our scRNA-seq data of Xrp1 O/E EEs have provided evidence on changes in gene expression profiles of each cell type by Xrp1 O/E in EEs.

2025-07-07 | GSE295684 | GEO

Spliceosome iCLIP

Project description:Spliceosome iCLIP

| PRJEB27592 | ENA