Human introns contain conserved tissue-specific cryptic poison exons
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1126174 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29478758_1.fastq.gz | Fastqsanger.gz | |||
| SRR29478758_2.fastq.gz | Fastqsanger.gz | |||
| SRR29478759_1.fastq.gz | Fastqsanger.gz | |||
| SRR29478759_2.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 4 of 4 |
Similar Datasets
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
Project description:Long non-coding RNAs (lncRNAs) are components of epigenetic control mechanisms that ensure appropriate and timely gene expression. The functions of lncRNAs are often mediated through associated gene regulatory activities, but how lncRNAs are distinguished from other RNAs and recruit effector complexes is unclear. Here we utilize the fission yeast Schizosaccharomyces pombe to investigate how lncRNAs engage silencing activities to regulate gene expression in cis. We find that invasion of lncRNA transcription into the downstream gene body incorporates a cryptic intron required for repression of that gene. Our analyses show that lncRNAs containing cryptic introns are targeted by the conserved Pir2ARS2 protein in association with splicing factors, which recruit RNA processing and chromatin modifying activities involved in gene silencing. Pir2 and splicing machinery are broadly required for gene repression. Our finding that human ARS2 also interacts with splicing factors suggests a conserved mechanism mediates gene repression through cryptic introns within lncRNAs.
2020-04-07 | PXD018373 | Pride
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
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 | GSE235083 | GEO
Project description:We investigated the ability of the NFkB protein p65 to bind RNA and what its target transcrips were. In this CLIP-seq experiment we demonstrated that p65 is capable of binding RNA and it has a preference to introns and exons, suggesting it binds unspliced RNA.
2022-03-08 | GSE197705 | GEO
Project description:Long non-coding RNAs (lncRNAs) dynamically regulate gene expression during development and in response to environmental conditions. In S. pombe, lncRNAs repress the expression of nearby genes via a mechanism involving silencing effector proteins. In this study, we find that invasion of a lncRNA into the neighboring gene results in inclusion of a cryptic intron that is required for its repressive activity. We show that cryptic introns are targeted by the conserved protein Pir2/ARS2 in association with splicing factors, which provide a scaffold for the recruitment of RNA degradation factors and chromatin modifying activities.
2020-04-07 | GSE135160 | GEO
Project description:Long non-coding RNAs (lncRNAs) dynamically regulate gene expression during development and in response to environmental conditions. In S. pombe, lncRNAs repress the expression of nearby genes via a mechanism involving silencing effector proteins. In this study, we find that invasion of a lncRNA into the neighboring gene results in inclusion of a cryptic intron that is required for its repressive activity. We show that cryptic introns are targeted by the conserved protein Pir2/ARS2 in association with splicing factors, which provide a scaffold for the recruitment of RNA degradation factors and chromatin modifying activities.
2020-04-07 | GSE135159 | GEO
Project description:Long non-coding RNAs (lncRNAs) dynamically regulate gene expression during development and in response to environmental conditions. In S. pombe, lncRNAs repress the expression of nearby genes via a mechanism involving silencing effector proteins. In this study, we find that invasion of a lncRNA into the neighboring gene results in inclusion of a cryptic intron that is required for its repressive activity. We show that cryptic introns are targeted by the conserved protein Pir2/ARS2 in association with splicing factors, which provide a scaffold for the recruitment of RNA degradation factors and chromatin modifying activities.
2020-04-07 | GSE135158 | GEO
Project description:Long non-coding RNAs (lncRNAs) dynamically regulate gene expression during development and in response to environmental conditions. In S. pombe, lncRNAs repress the expression of nearby genes via a mechanism involving silencing effector proteins. In this study, we find that invasion of a lncRNA into the neighboring gene results in inclusion of a cryptic intron that is required for its repressive activity. We show that cryptic introns are targeted by the conserved protein Pir2/ARS2 in association with splicing factors, which provide a scaffold for the recruitment of RNA degradation factors and chromatin modifying activities.
2020-04-07 | GSE135157 | GEO
Project description:The NFkB protein RELA/p65 binds predominantly transcript introns and exons
| PRJNA811611 | ENA