Similar Datasets
Project description:Poly (A) binding protein interacting protein 1 (PAIP1) has been shown to causally contribute to the development and progression of cancer. However, the biological function of PAIP1 in tumorigenesis remains largely unexplored. Here, we used RNA immunoprecipitation to map the interactions between PAIP1 and RNA on a genome wide level. A genome wide analysis showed that PAIP1 binding is specifically enriched in exon, intron and 3’ untranslated regions. The genes bound by PAIP1 were strongly associated with cancer-related pathways and we found that PAIP1 knockdown mediates the statistically significant regulation of alternative splice events. These data suggest that PAIP1 may influence alternative splicing and, using a VEGF-A minigene, we showed that overexpression of PAIP1 inhibits the expression of exon 6. Further analysis of PAIP1 showed that interacting proteins participate in splice factors, spliceosomes and exon junction complex assembly. Our work has demonstrated that PAIP1 has specific RNA binding properties that help to coordinate the isoform-specific expression of coding genes. These genes are associated with cancer, which suggests that PAIP1 is an important regulator of key cancer processes.
2022-05-05 | GSE150780 | GEO
Project description:Poly (A) binding protein interacting protein 1 (PAIP1) has been shown to causally contribute to the development and progression of cancer. However, the biological function of PAIP1 in tumorigenesis remains largely unexplored. Here, we used RNA immunoprecipitation to map the interactions between PAIP1 and RNA on a genome wide level. A genome wide analysis showed that PAIP1 binding is specifically enriched in exon, intron and 3’ untranslated regions. The genes bound by PAIP1 were strongly associated with cancer-related pathways and we found that PAIP1 knockdown mediates the statistically significant regulation of alternative splice events. These data suggest that PAIP1 may influence alternative splicing and, using a VEGF-A minigene, we showed that overexpression of PAIP1 inhibits the expression of exon 6. Further analysis of PAIP1 showed that interacting proteins participate in splice factors, spliceosomes and exon junction complex assembly. Our work has demonstrated that PAIP1 has specific RNA binding properties that help to coordinate the isoform-specific expression of coding genes. These genes are associated with cancer, which suggests that PAIP1 is an important regulator of key cancer processes.
2022-05-05 | GSE150779 | GEO
Project description:Identification of the RNA-protein interactions of PAIP1, which plays a novel role in alternative mRNA splicing
| PRJNA633557 | ENA
Project description:Identification of the RNA-protein interactions of PAIP1, which plays a novel role in alternative mRNA splicing (RIP-seq)
| PRJNA633561 | ENA
Project description:Identification of the RNA-protein interactions of PAIP1, which plays a novel role in alternative mRNA splicing (RNA-Seq)
| PRJNA633559 | ENA
Project description:Oncogenic metadherin is a key contributor to tumourigenesis with metadherin expression and cytoplasmic localisation previously linked to poor survival. A number of reports have shown metadherin localises specifically to nuclear speckles known to be rich in RNA-binding proteins including the splicing proteins YTHDC1, Sam68 and T-STAR, that have been shown to select alternative splice sites in mRNA of tumour-associated proteins including BRCA, MDM2 and VEGF. Here we investigate the interaction and relationship between metadherin and the splice factors YTHDC1, T-STAR and Sam68. Using a yeast two-hybrid assay and immunoprecipitation we show that metadherin interacts with YTHDC1, Sam68 and T-STAR and demonstrate that T-STAR is significantly overexpressed in prostate cancer tissue compared to benign prostate tissue. We also demonstrate that metadherin influences splice site selection in a dose-dependent manner in CD44v5-luc minigene reporter assays. Finally, we demonstrate that prostate cancer patients with higher metadherin expression have greater expression of the CD44v5 exon. CD44v5 expression could be used to discriminate patients with poor outcomes following radical prostatectomy. In this work we show for the first time that metadherin interacts with, and modulates, the function of key components of splicing associated with cancer development and progression.
| S-EPMC6770463 | biostudies-literature
Project description:Alternative splicing plays a major role in regulating the functional repertoire of the proteome. However, isoform-specific effects to protein-protein interactions (PPIs) are usually overlooked, making it impossible to judge the functional role of individual exons on a systems biology level. We overcome this barrier by integrating protein-protein interactions, domain-domain interactions and residue-level interactions information to lift exon expression analysis to a network level. Our user-friendly database DIGGER is available at https://exbio.wzw.tum.de/digger and allows users to seamlessly switch between isoform and exon-centric views of the interactome and to extract sub-networks of relevant isoforms, making it an essential resource for studying mechanistic consequences of alternative splicing.
| S-EPMC7778957 | biostudies-literature
Project description:Alternative pre-mRNA splicing is key to proteome diversity; however, the biological roles of alternative splicing (AS) in signaling pathways remain elusive. Here, we focus on TEA domain transcription factor 1 (TEAD1), a YAP binding factor in the Hippo signaling pathway. Public database analyses showed that expression of YAP-TEAD target genes negatively correlated with the expression of a TEAD1 isoform lacking exon 6 (TEAD1ΔE6) but did not correlate with overall TEAD1 expression. We confirmed that the transcriptional activity and oncogenic properties of the full-length TEAD1 isoform were greater than those of TEAD1ΔE6, with the difference in transcription related to YAP interaction. Furthermore, we showed that RNA-binding Fox-1 homolog 2 (RBFOX2) promoted the inclusion of TEAD1 exon 6 via binding to the conserved GCAUG element in the downstream intron. These results suggest a regulatory mechanism of RBFOX2-mediated TEAD1 AS and provide insight into AS-specific modulation of signaling pathways.
| S-EPMC9410899 | biostudies-literature
Project description:Aberrant RNA splicing is thought to play a key role in tumorigenesis. The assessment of its specific contributions is limited by the complexity of information derived from genome-wide array-based approaches. We describe how performing splicing factor-specific comparisons using both tumor and cell line data sets may more readily identify physiologically relevant tumor-specific splicing events. Affymetrix exon array data derived from glioblastoma (GBM) tumor samples with defined polypyrimidine tract-binding protein 1 (PTBP1) levels were compared with data from U251 GBM cells with and without PTBP1 knockdown. This comparison yielded overlapping gene sets that comprised only a minor fraction of each data set. The identification of a novel GBM-specific splicing event involving the USP5 gene led us to further examine its role in tumorigenesis. In GBM, USP5 generates a shorter isoform 2 through recognition of a 5' splice site within exon 15. Production of the USP5 isoform 2 was strongly correlated with PTBP1 expression in GBM tumor samples and cell lines. Splicing regulation was consistent with the presence of an intronic PTBP1 binding site and could be modulated through antisense targeting of the isoform 2 splice site to force expression of isoform 1 in GBM cells. The forced expression of USP5 isoform 1 in two GBM cell lines inhibited cell growth and migration, implying an important role for USP5 splicing in gliomagenesis. These results support a role for aberrant RNA splicing in tumorigenesis and suggest that changes in relatively few genes may be sufficient to drive the process.
| S-EPMC3319169 | biostudies-literature
Project description:Congenital heart disease (CHD) is a leading cause of death in children <1 year of age. Despite intense effort in the last 10 years, most CHDs (~70%) still have an unknown etiology. Conotruncal based defects, such as Tetralogy of Fallot (TOF), a common complex of devastating heart defects, typically requires surgical intervention in the first year of life. We reported that the noncoding transcriptome in myocardial tissue from children with TOF is characterized by significant variation in levels of expression of noncoding RNAs, and more specifically, a significant reduction in 12 small cajal body-associated RNAs (scaRNAs) in the right ventricle. scaRNAs are essential for the biochemical modification and maturation of small nuclear RNAs (spliceosomal RNAs), which in turn are critical components of the spliceosome. This is particularly important because we also documented that splicing of mRNAs that are critical for heart development was dysregulated in the heart tissue of infants with TOF. Furthermore, we went on to show, using the zebrafish model, that altering the expression of these same scaRNAs led to faulty mRNA processing and heart defects in the developing embryo. This review will examine how scaRNAs may influence spliceosome fidelity in exon retention during heart development and thus contribute to regulation of heart development.
| S-EPMC6023535 | biostudies-literature