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An anciently diverged family of RNA binding proteins maintain correct splicing of ultra-long exons through cryptic splice site repression

ABSTRACT: An anciently diverged family of RNA binding proteins maintain correct splicing of ultra-long exons through cryptic splice site repression

PROVIDER: PRJNA976356 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12744038_1.fastq.gz	Fastqsanger.gz
	SRR12744038_2.fastq.gz	Fastqsanger.gz
	SRR12744039_1.fastq.gz	Fastqsanger.gz
	SRR12744039_2.fastq.gz	Fastqsanger.gz
	SRR12744040_1.fastq.gz	Fastqsanger.gz

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An anciently diverged family of RNA binding proteins maintain correct splicing of ultra-long exons through cryptic splice site repression [RNA-seq]

Project description:We previously showed that the germ cell specific nuclear protein RBMXL2 represses cryptic splicing patterns during meiosis and is required for male fertility. RBMXL2 evolved from the X-linked RBMX gene, which is silenced during meiosis due to sex chromosome inactivation. It has been unknown whether RBMXL2 provides a direct replacement for RBMX in meiosis, or whether RBMXL2 evolved to deal with the transcriptionally permissive environment of meiosis. Here we find that RBMX primarily operates as a splicing repressor in somatic cells, and specifically regulates a distinct class of exons that exceed the median human exon size. RBMX protein-RNA interactions are enriched within ultra-long exons, particularly within genes involved in genome stability, and repress the selection of cryptic splice sites that would compromise gene function. These similarities in overall function suggested that RBMXL2 might replace the function of RBMX during meiosis. To test this prediction we carried out inducible expression of RBMXL2 and the more distantly related RBMY protein in somatic cells, finding each could rescue aberrant patterns of RNA processing in response to RBMX depletion. The C-terminal disordered domain of RBMXL2 is sufficient to rescue proper splicing control after RBMX depletion. Our data indicate that RBMX and RBMXL2 have parallel roles in somatic tissues and the germline that must have have been conserved over at least 200 million years of mammalian evolution. We propose RBMX family proteins are particularly important for the splicing inclusion of ultra-long exons because these would be particularly susceptible to disruption by cryptic splice site selection.

2023-09-28 | GSE158770 | GEO

An anciently diverged family of RNA binding proteins maintain correct splicing of ultra-long exons through cryptic splice site repression [iCLIP-seq]

2023-09-28 | GSE233497 | GEO

An anciently diverged family of RNA binding proteins maintain correct splicing of ultra-long exons through cryptic splice site repression [iCLIP-seq]

Project description:An anciently diverged family of RNA binding proteins maintain correct splicing of ultra-long exons through cryptic splice site repression [iCLIP-seq]

| PRJNA976358 | ENA

An anciently diverged family of RNA binding proteins maintain correct splicing of ultra-long exons through cryptic splice site repression [RNA-seq]

Project description:An anciently diverged family of RNA binding proteins maintain correct splicing of ultra-long exons through cryptic splice site repression [RNA-seq]

| PRJNA666447 | ENA

An anciently diverged family of RNA binding proteins maintain correct splicing of ultra-long exons through cryptic splice site repression

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-09-28 | GSE233498 | GEO

Identification of differentially regulated splice variants and novel exons in glial brain tumors using exon arrays

Project description:Aberrant splice variants are involved in the initiation and/or progression of glial brain tumors. We therefore set out to identify splice variants that are differentially expressed between histological subgroups of gliomas. Splice variants were identified using a novel platform that profiles the expression of virtually all known and predicted exons present in the human genome. Exon-level expression profiling was performed on 26 glioblastomas, 22 oligodendrogliomas and 6 control brain samples. Our results demonstrate that Human Exon arrays can identify subgroups of gliomas based on their histological appearance and genetic aberrations. We next used our expression data to identify differentially expressed splice variants. In two independent approaches, we identified 49 and up to 459 exons that are differentially spliced between glioblastomas and oligodendrogliomas a subset of which (47% and 33%) were confirmed by RT-PCR. In addition, exon-level expression profiling also identified >700 novel exons. Expression of ~67% of these candidate novel exons was confirmed by RT-PCR. Our results indicate that exon-level expression profiling can be used to molecularly classify brain tumor subgroups, can identify differentially regulated splice variants and can identify novel exons. The splice variants identified by exon-level expression profiling may help to detect the genetic changes that cause or maintain gliomas and may serve as novel treatment targets. Keywords: cell type comparison 6 adult non diseased brain, 26 glioblastomas, 21 oligodendrogliomas

2008-01-28 | E-GEOD-9385 | biostudies-arrayexpress

Identification of differentially regulated splice variants and novel exons in glial brain tumors using exon arrays

2008-01-29 | GSE9385 | GEO

Human introns contain conserved tissue-specific cryptic poison exons

Project description:Eukaryotic cells express a large number of transcripts from a single gene due to alternative splicing. Despite hundreds of thousands of splice isoforms being annotated in databases, it has been reported that the current exon catalogs remain incomplete. At the same time, introns of human protein-coding genes contain a large number of evolutionarily conserved elements with unknown function. Here, we explore the possibility that some of them represent cryptic exons that are expressed in rare conditions. We identified a group of cryptic exons that are similar to the annotated exons in terms of evolutionary conservation and RNA-seq read coverage in the GTEx dataset. Most of them were poison, i.e. generated an NMD isoform upon inclusion, and many showed signs of tissue-specific and cancer-specific expression and regulation. We performed RNA-seq in A549 cell line treated with cycloheximide to inactivate NMD, and confirmed using qPCR that seven of eight exons tested are, indeed, expressed. This study shows that introns of human protein-coding genes contain cryptic poison exons, which reside in conserved intronic regions and remain not fully annotated due to insufficient representation in RNA-seq libraries.

2024-11-20 | GSE270310 | GEO

Knockout of circRNAs by base editing back-splice sites of circularized exons

Project description:Knockout of circRNAs by base editing back-splice sites of circularized exons

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Mouse Alt-Splice Tissue Panel (Brain vs Non-Brain)

Project description:22 Normal adult mouse tissues on custom alternative transcript sensitive Affymetrix microarray used to address differeneces in tissue specific alternative splicing. Abstract: Alternative splicing contributes to both gene regulation and protein diversity. To discover broad relationships between regulation of alternative splicing and sequence conservation, we applied a systems approach, using oligonucleotide microarrays designed to capture splicing information across the mouse genome. In a set of 22 adult tissues, we observe expression of RNA containing at least two alternative splice junctions for about a third of the 3200 alternative events we could detect. Statistical comparisons identify 171 cassette exons whose inclusion or skipping is different in brain relative to other tissues, and another 28 exons whose splicing is different in muscle. A subset of these exons is associated with unusual blocks of intron sequence whose conservation in vertebrates rivals that of protein-coding exons. By focusing on sets of exons with similar regulatory patterns, we have identified new sequence motifs implicated in brain and muscle splicing regulation. Of note is a motif strikingly similar to the branchpoint consensus, but which is located downstream of the 5' splice site of exons included in muscle. Analysis of three paralogous membrane-associated guanylate kinase (MAGUK) genes reveals that each contains a paralogous tissue regulated exon with a similar tissue inclusion pattern. While the intron sequences flanking these exons remain highly conserved among mammalian orthologs, the paralogous flanking intron sequences have diverged considerably, suggesting unusually complex evolution of the regulation of alternative splicing in multigene families. Keywords: Alternative splicing isoform specific, adult mouse tissues

2006-01-19 | GSE3063 | GEO

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