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STRAP-dependent alternative splicing events; STRAP-RNA interactions in mouse early embryo and lineage-committed cells.

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE131474 | GEO | 2020/09/16

REPOSITORIES: GEO

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STRAP-dependent alternative splicing events STRAP-RNA interactions in mouse early embryo and lineage-committed cells.

Project description:STRAP-dependent alternative splicing events STRAP-RNA interactions in mouse early embryo and lineage-committed cells.

| PRJNA543786 | ENA

Transcriptome-wide maps of STRAP-RNA interactions in mouse early embryo and lineage-committed cells.

Project description:We report the application of enhanced cross-linking immunoprecipitation (eCLIP) sequencing technology for high-throughput profiling of STRAP-RNA interactions in mouse embryos (E9.5) or embryoid body (EB) cells. Based on the eCLIP-seq data, we computationally identified a transcriptome-wide set of high-confidence peaks (over ten thousands) and most of STRAP-peaks distributed in the murine genome by defining certain exons and introns as well as their intersection. STRAP eCLIP signals in embryos were dramatically enriched at exon/intron and intron/exon borders. Numerous STRAP peaks are significantly enriched on the genes with critical roles in early organ development. Finally, we show two examples of STRAP-RNA binding that link to its regulated genes at the alternative splicing level. Together, we uncover the position- and context- dependent effects of STRAP on splicing regulation during mouse embryonic stem cells lineage commitment. Our studies provide a very useful platform to decipher STRAP’s role in the many steps in RNA biogenesis for future studies.

2020-09-16 | GSE131472 | GEO

Next generation sequencing facilitates quantitative analysis of STRAP-dependent alternative splicing events

Project description:We report the application of next generation sequencing for evaluating alternative splicing (AS) events on lineage-committed WT and Strap-KO embryoid body (EB) cells. We also analyzed AS during mouse embryo development using RNA-seq data. Of all STRAP-regulated AS, exon-skipping events were the most frequent ones with significant changes in 49% (240 out of 489) cases. Retained introns were also overrepresented (20%, 97 out of 489) as compared to other types of AS STRAP appears to function in promoting both exon inclusion and skipping at different exons. GO function revealed STRAP-regulated AS events involve in protein catabolism, molecular binding and cell motility. More specifically, they included neuronal migration and development. Together, these analyses uncovered the previous unknown role of STRAP involved in the substantial transcriptional diversity at the exon level in certain development stage. Our study also represents the first detailed analysis of AS events in the mouse early organogenesis with biologic replicates, generated by RNA-seq technology.

2020-09-16 | GSE131471 | GEO

STRAP regulates alternative splicing fidelity during lineage commitment of mouse embryonic stem cells.

Project description:Alternative splicing (AS) is involved in cell fate decisions and embryonic development. However, regulation of these processes is poorly understood. Here, we have identified the serine threonine kinase receptor-associated protein (STRAP) as a putative spliceosome-associated factor. Upon Strap deletion, there are numerous AS events observed in mouse embryoid bodies (EBs) undergoing a neuroectoderm-like state. Global mapping of STRAP-RNA binding in mouse embryos by enhanced-CLIP sequencing (eCLIP-seq) reveals that STRAP preferably targets transcripts for nervous system development and regulates AS through preferred binding positions, as demonstrated for two neuronal-specific genes, Nnat and Mark3. We have found that STRAP involves in the assembly of 17S U2 snRNP proteins. Moreover, in Xenopus, loss of Strap leads to impeded lineage differentiation in embryos, delayed neural tube closure, and altered exon skipping. Collectively, our findings reveal a previously unknown function of STRAP in mediating the splicing networks of lineage commitment, alteration of which may be involved in early embryonic lethality in mice.

| S-EPMC7684319 | biostudies-literature

Position-dependent FUS-RNA interactions regulate alternative splicing events and transcriptions.

Project description:FUS is an RNA-binding protein that regulates transcription, alternative splicing, and mRNA transport. Aberrations of FUS are causally associated with familial and sporadic ALS/FTLD. We analyzed FUS-mediated transcriptions and alternative splicing events in mouse primary cortical neurons using exon arrays. We also characterized FUS-binding RNA sites in the mouse cerebrum with HITS-CLIP. We found that FUS-binding sites tend to form stable secondary structures. Analysis of position-dependence of FUS-binding sites disclosed scattered binding of FUS to and around the alternatively spliced exons including those associated with neurodegeneration such as Mapt, Camk2a, and Fmr1. We also found that FUS is often bound to the antisense RNA strand at the promoter regions. Global analysis of these FUS-tags and the expression profiles disclosed that binding of FUS to the promoter antisense strand downregulates transcriptions of the coding strand. Our analysis revealed that FUS regulates alternative splicing events and transcriptions in a position-dependent manner.

| S-EPMC3402842 | biostudies-literature

Transcriptome-wide maps of STRAP-RNA interactions in mouse early embryo and lineage-committed cells.

Project description:Transcriptome-wide maps of STRAP-RNA interactions in mouse early embryo and lineage-committed cells.

| PRJNA543791 | ENA

STRAP regulates alternative splicing fidelity during lineage commitment of mouse embryonic stem cells

Project description:STRAP protein was IP'd and corresponding binding proteins were identified by high resolution nanoLCMS2 vs a control experiment.

2020-09-10 | PXD015371 | Pride

Next generation sequencing facilitates quantitative analysis of STRAP-dependent alternative splicing events

Project description:Next generation sequencing facilitates quantitative analysis of STRAP-dependent alternative splicing events

| PRJNA543790 | ENA

Position-dependent alternative splicing activity revealed by global profiling of alternative splicing events regulated by PTB.

Project description:To gain global insights into the role of the well-known repressive splicing regulator PTB, we analyzed the consequences of PTB knockdown in HeLa cells using high-density oligonucleotide splice-sensitive microarrays. The major class of identified PTB-regulated splicing event was PTB-repressed cassette exons, but there was also a substantial number of PTB-activated splicing events. PTB-repressed and PTB-activated exons showed a distinct arrangement of motifs with pyrimidine-rich motif enrichment within and upstream of repressed exons but downstream of activated exons. The N-terminal half of PTB was sufficient to activate splicing when recruited downstream of a PTB-activated exon. Moreover, insertion of an upstream pyrimidine tract was sufficient to convert a PTB-activated exon to a PTB-repressed exon. Our results show that PTB, an archetypal splicing repressor, has variable splicing activity that predictably depends upon its binding location with respect to target exons.

| S-EPMC2933513 | biostudies-literature

Transcriptome analysis of alternative splicing events regulated by SRSF10 reveals position-dependent splicing modulation.

Project description:Splicing factor SRSF10 is known to function as a sequence-specific splicing activator. Here, we used RNA-seq coupled with bioinformatics analysis to identify the extensive splicing network regulated by SRSF10 in chicken cells. We found that SRSF10 promoted both exon inclusion and exclusion. Motif analysis revealed that SRSF10 binding to cassette exons was associated with exon inclusion, whereas the binding of SRSF10 within downstream constitutive exons was associated with exon exclusion. This positional effect was further demonstrated by the mutagenesis of potential SRSF10 binding motifs in two minigene constructs. Functionally, many of SRSF10-verified alternative exons are linked to pathways of stress and apoptosis. Consistent with this observation, cells depleted of SRSF10 expression were far more susceptible to endoplasmic reticulum stress-induced apoptosis than control cells. Importantly, reconstituted SRSF10 in knockout cells recovered wild-type splicing patterns and considerably rescued the stress-related defects. Together, our results provide mechanistic insight into SRSF10-regulated alternative splicing events in vivo and demonstrate that SRSF10 plays a crucial role in cell survival under stress conditions.

| S-EPMC3973337 | biostudies-literature

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