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An essential role for the ultra-conserved poison exon of Tra2b in fertility in mice

ABSTRACT: An essential role for the ultra-conserved poison exon of Tra2b in fertility in mice

PROVIDER: PRJNA984307 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24941037.fastq.gz	Fastqsanger.gz
	SRR24941038.fastq.gz	Fastqsanger.gz
	SRR24941039.fastq.gz	Fastqsanger.gz
	SRR24940266_1.fastq.gz	Fastqsanger.gz
	SRR24940266_2.fastq.gz	Fastqsanger.gz

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Similar Datasets

An essential role for the ultra-conserved poison exon of Tra2b in fertility in mice (RNA-seq)

Project description:Alternative splicing-induced inclusion of poison exons containing in-frame stop codons is a mechanism that can be used to attenuate gene expression. Poison exon have been implicated in cancer, but how they operate within the context of normal development and physiology is poorly understood. Several splicing regulator genes, including Tra2b, contain ultra-conserved poison exons that function within regulatory loops to fine-tune their activity. To investigate the physiological role of poison exons in vivo, we created mice lacking either Tra2b or its poison exon, specifically during spermatogenesis to reveal both are essential for male fertility. The mouse Tra2b gene is essential for mitotic proliferation of germ cells, whereas, in contrast, the Tra2b poison exon is critically required during meiosis and not needed by mitotically proliferating cell populations within the germline. Poison exon deletion causes infertility, with a block in male meiotic prophase where Tra2β protein expression levels normally increase. Deletion of the Tra2b poison exon changes expression patterns of genes important for meiosis and splicing patterns of Tra2β target exons, suggesting Tra2b poison exon splicing prevents meiotic cells accumulating toxic levels of Tra2b expression. Our data provide a new physiological explanation for Tra2b poison exon ultra-conservation and indicate the importance of evaluating poison exon function within a physiological context.

2024-12-19 | GSE235084 | GEO

An essential role for the ultra-conserved poison exon of Tra2b in fertility in mice (iCLIP-seq)

2024-12-19 | GSE235083 | GEO

An essential role for the ultra-conserved poison exon of Tra2b in fertility in mice (RNA-seq)

Project description:An essential role for the ultra-conserved poison exon of Tra2b in fertility in mice (RNA-seq)

| PRJNA984310 | ENA

An essential role for the ultra-conserved poison exon of Tra2b in fertility in mice (iCLIP-seq)

Project description:An essential role for the ultra-conserved poison exon of Tra2b in fertility in mice (iCLIP-seq)

| PRJNA984309 | ENA

An essential role for the ultra-conserved poison exon of Tra2b in fertility in mice

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

2024-12-19 | GSE235085 | GEO

An ultra-conserved poison exon in the Tra2b gene encoding a splicing activator is essential for male fertility and meiotic cell division.

Project description:The cellular concentrations of splicing factors (SFs) are critical for controlling alternative splicing. Most serine and arginine-enriched (SR) protein SFs regulate their own concentration via a homeostatic feedback mechanism that involves regulation of inclusion of non-coding 'poison exons' (PEs) that target transcripts for nonsense-mediated decay. The importance of SR protein PE splicing during animal development is largely unknown despite PE ultra-conservation across animal genomes. To address this, we used mouse genetics to disrupt an ultra-conserved PE in the Tra2b gene encoding the SR protein Tra2β. Focussing on germ cell development, we found that Tra2b PE deletion causes azoospermia due to catastrophic cell death during meiotic prophase. Failure to proceed through meiosis was associated with increased Tra2b expression sufficient to drive aberrant Tra2β protein hyper-responsive splice patterns. Although critical for meiotic prophase, Tra2b PE deletion spared earlier mitotically active germ cells, even though these still required Tra2b gene function. Our data indicate that PE splicing control prevents the accumulation of toxic levels of Tra2β protein that are incompatible with meiotic prophase. This unexpected connection with male fertility helps explain Tra2b PE ultra-conservation and indicates the importance of evaluating PE function in animal models.

| S-EPMC11791180 | biostudies-literature

An ultra-conserved poison exon in the Tra2b gene encoding a splicing activator is essential for male fertility and meiotic cell division

Project description:The cellular concentrations of splicing factors (SFs) are critical for controlling alternative splicing. Most serine and arginine-enriched (SR) protein SFs regulate their own concentration via a homeostatic feedback mechanism that involves regulation of inclusion of non-coding 'poison exons' (PEs) that target transcripts for nonsense-mediated decay. The importance of SR protein PE splicing during animal development is largely unknown despite PE ultra-conservation across animal genomes. To address this, we used mouse genetics to disrupt an ultra-conserved PE in the Tra2b gene encoding the SR protein Tra2β. Focussing on germ cell development, we found that Tra2b PE deletion causes azoospermia due to catastrophic cell death during meiotic prophase. Failure to proceed through meiosis was associated with increased Tra2b expression sufficient to drive aberrant Tra2β protein hyper-responsive splice patterns. Although critical for meiotic prophase, Tra2b PE deletion spared earlier mitotically active germ cells, even though these still required Tra2b gene function. Our data indicate that PE splicing control prevents the accumulation of toxic levels of Tra2β protein that are incompatible with meiotic prophase. This unexpected connection with male fertility helps explain Tra2b protein PE ultra-conservation and indicates the importance of evaluating PE function in animal models.

| S-SCDT-10_1038-S44318-024-00344-6 | biostudies-other

Splicing and gene expression changes in cell lines treated with splicing switching oligonucleotide targeting TRA2B

Project description:RNA-sequencing data from MDA-MB231 breast cancer cells, U87MG glioblastoma cells, and mouse breast cancer PDX models treated with antisense oligonucleotides targeting exon 2 of TRA2B. Additionally, RNA-sequencing data from MDA-MB231 breast cancer cells and U87MG glioblastoma cells treated with siRNAs targeting TRA2B. RNA-sequencing data from MDA-MB231 breast cancer cells nad U87MG glioblastoma cells treated with antisense oligonucleotides targeting exon 2 of TRA2B.

2024-12-20 | GSE231555 | GEO

Neuronal-specific Deficiency of the Splicing Factor Tra2b Causes p21-mediated Apoptosis in Neurogenic Areas of the Developing Mouse Brain

Project description:Alternative splicing (AS) increases the informational content of the genome and is more prevalent in the brain than in any other tissue. The splicing factor Tra2b (Sfrs10) can modulate splicing inclusion of exons by specifically detecting GAA-rich binding motifs and its absence causes early embryonic lethality in mice. TRA2B has been shown to be involved in splicing processes of Nasp (nuclear autoantigenic sperm protein), MAPT (microtubule associated protein tau) and SMN (survival motor neuron), and is therefore implicated in spermatogenesis and neurological diseases like AlzheimerM-^Rs disease, dementia, ParkinsonM-^Rs disease and spinal muscular atrophy. Here we generated a neuronal-specific Tra2b knock-out mouse that lacks Tra2b expression in neuronal and glial precursor cells by using the Nestin-Cre. Neuronal-specific Tra2b knock-out mice die immediately after birth and show severe abnormalities in cortical development, which are caused by massive apoptotic events in the ventricular layers of the cortex, demonstrating a pivotal role of Tra2b for the developing central nervous system. Using whole brain RNA on exon arrays we identified differentially expressed alternative exons of Tubulin?1 and Shugoshin like2 as in vivo targets of Tra2b. Most interestingly, we found increased expression of the cyclin dependent kinase inhibitor 1a (p21) which we could functionally link to neuronal precursor cells in the affected brain regions. We provide further evidence that the absence of Tra2b causes p21 upregulation and ultimately cell death in NSC34 neuronal-like cells. These findings demonstrate that Tra2b regulates splicing events essential for maintaining neuronal viability during development. Apoptotic events triggered via p21 might not be restricted to the developing brain but could possibly be generalized to the whole organism and explain early embryonic lethality in Tra2b-depleted mice.

2013-12-16 | E-MTAB-2157 | biostudies-arrayexpress

Tra2b's Ultraconserved Poison Exon relays TCR stimulation to shape T cell fate [PEKOSeq]

Project description:Analysis of transcript changes with enough depth for evaluation of splicing changes between scrambled control CD8+ T or Tra2b-PE KO CD8+ T cells from mice

2024-06-01 | GSE267601 | GEO

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