Exon-activated functional rescue secures neuronal transcript signatures
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA612625 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11307600_1.fastq.gz | Fastqsanger.gz | |||
| SRR11307600_2.fastq.gz | Fastqsanger.gz | |||
| SRR11307601_1.fastq.gz | Fastqsanger.gz | |||
| SRR11307601_2.fastq.gz | Fastqsanger.gz | |||
| SRR11307602_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 122 |
Similar Datasets
Project description:The production of alternative RNA variants contributes to the tissue-specific regulation of gene expression. In the animal nervous system, a shift towards more distal 3’ processing sites generates hundreds of substantially extended messenger RNAs. These neuronal transcript signatures are crucial for nervous system development and function. However, no clear understanding of the mechanism of systematic 3’ extension in neurons has yet been achieved. Here, we report that the highly conserved RNA-binding protein ELAV globally regulates all events of neuronal 3’ end processing by directly binding to the proximal 3’ end of its target RNAs. We uncover an endogenous strategy of functional gene rescue, by which neuronal RNA signatures are safeguarded in a loss-of-function context. When not directly repressed by ELAV, the transcript encoding the ELAV paralogue FNE acquires a mini‑exon, which equips the new FNE protein with the ability to translocate to the nucleus and rescue neuronal 3’ end processing. We propose that exon-activated functional rescue is a widespread mechanism that ensures robustness of processes that are regulated by a hierarchy, rather than by redundancy, of effectors.
2020-10-01 | GSE146986 | GEO
Project description:Background: Neuronal cells respond to changes in intracellular Ca2+ ([Ca2+]i) by affecting both the abundance and the architecture of specific mRNAs. While Ca2+-induced transcription and transcript variation have both been recognized as important sources of gene regulation, the interplay of these two phenomena has not been evaluated together on a genome scale. Results: Here, we show that exon-centric microarrays can be used to resolve the Ca2+-modulated gene expression response into transcript-level and exon-level regulation. Global assessments of affected transcripts reveal modulation within distinct functional gene categories. We find that transcripts containing Ca2+-modulated exons show enrichment for Ca2+-ion binding, calmodulin-binding, plasma membrane-associated, and metabolic proteins. Additionally, we uncover instances of regulated exon use in potassium channels, neuroendocrine secretory proteins, and in metabolic enzymes, and demonstrate that regulated changes in exon expression give rise to distinct transcript isoforms. Conclusions: Our findings connect extracellular stimuli to specific exon behavior and suggest that changes in transcript and exon abundance are reflective of a coordinated gene expression response to elevated [Ca2+]i. The technology we describe here lends itself readily to the resolution of stimulus-induced gene expression at both the transcript and exon levels. Keywords: Ca2+-modulated exons and transcripts
2007-09-24 | GSE6976 | GEO
Project description:Neuronal activity regulates alternative exon usage
| PRJNA622919 | ENA
Project description:In order to identify genes with different overall transcript levels or differential exon levels (alternative processing) between the groups Control and Tat-SF1KD, we studied 11 hybridizations on the HumanExon10ST array using mixed model analysis of variance. 526 genes with significant transcript level differences between the groups and 1397 genes with significant differential exon levels were found, including 99 genes with both transcript and exon level differences (p<0.01).
2011-02-16 | GSE19927 | GEO
Project description:Partial rescue of neuronal genes deregulated in CdLS by cohesin
| PRJNA631234 | ENA
Project description:Cell-type-specific gene regulatory programs are crucial for cell differentiation and function. In animal neurons, the highly conserved ELAV/Hu family of proteins promotes alternative splicing and alternative polyadenylation of mRNA precursors to create unique neuronal transcript isoforms. Here, we show in Drosophila that the ELAV-mediated establishment of neuron-specific mRNA isoforms at the onset of neuronal differentiation constitutes a developmental bottleneck. While ELAV loss during a critical developmental time window is lethal and cannot be rescued later by the activation of the ELAV-like paralogue FNE, loss of ELAV function outside of that window results in neurological defects of differing nature and degree. FNE can effectively perform all molecular functions of ELAV, and, when activated early enough, fully rescue neuronal development. Our findings demonstrate the essential role of robust ELAV activity and intact neuronal signatures in the differentiation and function of the nervous system.
2022-11-15 | GSE199714 | GEO
Project description:The human Factor VIII (F8) protein is essential for the blood coagulation cascade and specific F8 mutations cause the rare bleeding disorder Hemophilia A (HA). Here, we investigated the impact of HA-causing single-nucleotide mutations on F8 pre-mRNA splicing. We found that 14/97 (∼14.4%) coding sequence mutations tested in our study induced exon skipping. Splicing patterns of 4/11 (∼36.4%) F8 exons tested were especially sensitive to the presence of common disease-causing mutations. RNA-chemical probing analyses revealed a three-way junction structure at the 3′ end of intron 15 (TWJ-3-15). TWJ-3-15 sequesters the polypyrimidine tract, a key determinant of 3′ splice site strength. Using exon-16 of the F8 gene as a model, we designed specific antisense oligonucleotides (ASOs) that target TWJ-3-15 and identified three that promote the splicing of F8 exon-16. Interaction of TWJ-3-15 with ASOs increases accessibility of the polypyrimidine tract and inhibits the binding of hnRNPA1-dependent splicing silencing factors. Moreover, ASOs targeting TWJ-3-15 rescue diverse splicing-sensitive HA-causing mutations, most of which are distal to the 3’ splice site being impacted. The TWJ-3-15 structure and its effect on mRNA splicing provide a model for HA etiology in patients harboring specific F8 mutations and provide a framework for precision RNA-based HA therapies.
2024-01-17 | GSE230495 | GEO
Project description:Investigation of whole genome expression profiles during four time points during the intraerythrocytic lifecycle of the malaria parasite Plasmodium falciparum for transcript isoforms using Exon Arrays. The samples used in this study are further described in Turnbull et. al., Simultaneous Genome-Wide Gene Expression and Transcript Isoform Profiling in the Human Malaria Parasite (in review)
2017-12-31 | GSE86254 | GEO
Project description:Investigation of whole genome expression profiles during four time points during the intraerythrocytic lifecycle of the malaria parasite Plasmodium falciparum for transcript isoforms using Exon Arrays. The samples used in this study are further described in Turnbull et. al., Simultaneous Genome-Wide Gene Expression and Transcript Isoform Profiling in the Human Malaria Parasite (in review)
2017-12-31 | GSE85248 | GEO
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