The landscape of alternative splicing in aggressive prostate cancers
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA594270 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11960812_1.fastq.gz | Fastqsanger.gz | |||
| SRR11960812_2.fastq.gz | Fastqsanger.gz | |||
| SRR11960813_1.fastq.gz | Fastqsanger.gz | |||
| SRR11960813_2.fastq.gz | Fastqsanger.gz | |||
| SRR11960814_1.fastq.gz | Fastqsanger.gz |
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Project description:We sought to define the landscape of alternative pre-mRNA splicing in prostate cancers and the relationship of exon choice to known genetic driver alterations. To do so, we compiled a meta-dataset comprised of RNA-Seq samples from publicly available sources representing a range of phenotypes from normal tissue to drug resistant metastases. We subjected these samples to exon-level analysis with purpose-built software. We then correlated transcriptional signatures of cancer driver pathways with these alternative splicing events and discovered that Myc signaling was correlated with incorporation of a set of cassette exons found in RNA binding proteins. We experimentally verified this finding in a human prostate cell transformation assay. Our results connect changes in alternative pre-mRNA splicing to oncogenic alterations common in prostate and many other cancers. We also establish a role for Myc in regulating RNA processing by controlling the incorporation of nonsense mediated decay-determinant exons in RNA binding proteins.
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Project description:Therapeutic targeting of splicing in aggressive prostate cancer
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Project description:We sought to define the landscape of alternative pre-mRNA splicing in prostate cancers and the relationship of exon choice to known cancer driver alterations. To do so, we compiled a metadataset composed of 876 RNA-sequencing (RNA-Seq) samples from five publicly available sources representing a range of prostate phenotypes from normal tissue to drug-resistant metastases. We subjected these samples to exon-level analysis with rMATS-turbo, purpose-built software designed for large-scale analyses of splicing, and identified 13,149 high-confidence cassette exon events with variable incorporation across samples. We then developed a computational framework, pathway enrichment-guided activity study of alternative splicing (PEGASAS), to correlate transcriptional signatures of 50 different cancer driver pathways with these alternative splicing events. We discovered that Myc signaling was correlated with incorporation of a set of 1,039 cassette exons enriched in genes encoding RNA binding proteins. Using a human prostate epithelial transformation assay, we confirmed the Myc regulation of 147 of these exons, many of which introduced frameshifts or encoded premature stop codons. Our results connect changes in alternative pre-mRNA splicing to oncogenic alterations common in prostate and many other cancers. We also establish a role for Myc in regulating RNA splicing by controlling the incorporation of nonsense-mediated decay-determinant exons in genes encoding RNA binding proteins.
| S-EPMC7071906 | biostudies-literature
Project description:Circular RNA (circRNA) is a group of RNA family generated by RNA circularization, which was discovered ubiquitously across different cancers. However, the internal structure of circRNA is hard to be determined since of the alternative splicing happened in exons and introns of circRNA and the cancer-specific alternative splicing of circRNA is less to be identified. Here we proposed a custom tool CircSplice, which could identify internal alternative splicing of circRNA and compare the differential splicing between samples. By applying CircSplice in ccRCC, we identified cancer-specific alternative splicing (AS) events belong to circRNAs in ccRCC. We further confirmed the existence of alternative splicing events in circRNAs by RT-PCR. This study is the first exploration of cancer-specific alternative splicing in circRNAs, which helps researchers to better understand potential functions of splicing of circRNAs in cancers.
2019-03-11 | GSE124453 | GEO
Project description:Analysis of the maize alternative splicing landscape, including transcript discovery and mapping of genotype-dependent variations in alternative splicing using B73, Mo17 and the SX19 inbred mapping population Total RNA was isolated from 5 week old leaves of hydroponically grown maize plants and used to construct RNA seq libraries
2014-10-29 | E-GEOD-57337 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE23513: Position-dependent alternative splicing activity revealed by global profiling of alternative splicing events regulated by PTB (HJAY) GSE23514: Position-dependent alternative splicing activity revealed by global profiling of alternative splicing events regulated by PTB (Exon array) Refer to individual Series
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Project description:Alternative splicing (AS) is a key regulatory mechanism that contributes to transcriptome and proteome diversity. As very few genome-wide studies analyzing AS in plants are available, we have performed high-throughput sequencing of a normalized cDNA library which resulted in a high coverage transcriptome map of Arabidopsis. We detect ~150,000 splice junctions derived mostly from typical plant introns, including a large number of U12 introns (2,069). Around 61% of multi-exonic genes are alternatively spliced under normal growth conditions. These values are much higher than previously reported and imply a significant role of AS in Arabidopsis transcriptome complexity. Moreover we provide experimental validation of 540 AS transcripts (from 256 genes coding for important regulatory factors) using high resolution RT-PCR and Sanger sequencing. Intron retention (IR) is the most frequent AS event (~40%) but many IRs have relatively low read coverage and are less well represented in assembled transcripts. Additionally ~51% of Arabidopsis genes produce AS transcripts which do not involve IR. Therefore the significance of IR in generating transcript diversity is in general overestimated. IR analysis allowed the identification of a large set of cryptic introns inside annotated exons. Importantly 29% of these cryptic introns are in frame indicating a role in protein diversity. Furthermore we show extensive AS coupled to nonsense-mediated decay in AFC2, encoding a highly conserved LAMMER kinase which phosphorylates splicing factors, thus establishing a complex loop in AS regulation. We provide the most comprehensive analysis of AS to date which will serve as a valuable resource for the plant community to study transcriptome complexity and gene regulation.
2012-03-10 | E-MTAB-4288 | biostudies-arrayexpress
Project description:We studied the alternative splicing function of KDM4B and found that KDM4B can act as a bona fide trans-acting splicing factor that binds RNA and signal-responsive scaffold protein that binds spliceosome.
2020-04-01 | GSE130620 | GEO
Project description:Alternative polyadenylation has been implicated as an important regulator of gene expression. In some cases, alternative polyadenylation is known to couple with alternative splicing to influence last intron removal. However, it is unknown whether alternative polyadenylation events influence alternative splicing decisions at upstream exons. Knockdown of the polyadenylation factors CFIm25 or CstF64 was used as an approach in identifying alternative polyadenylation and alternative splicing events on a genome-wide scale. Although hundreds of alternative splicing events were found to be differentially spliced in the knockdown of CstF64, genes associated with alternative polyadenylation did not exhibit an increased incidence of alternative splicing. These results demonstrate that the coupling between alternative polyadenylation and alternative splicing is usually limited to defining the last exon. The striking influence of CstF64 knockdown on alternative splicing can be explained through its effects on UTR selection of known splicing regulators such as hnRNP A2/B1, thereby indirectly influencing splice site selection. We conclude that changes in the expression of the polyadenylation factor CstF64 influences alternative splicing through indirect effects. HeLa cell line was stably transfected with shRNA plasmids targeting CstF64. Total RNA was isolated from CstF64 KD cells and wild-type control cells using Trizol according to manufacturerâs protocols. Samples were deep sequenced in duplicate using the Illumina GAIIx system.
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