Similar Datasets
Project description:Our study aimed to explore how DEK, a carcinogenic protein with chromatin architectural function, genome-widely binds to RNA and affects the alternative splicing in cancer cells to decipher its molecular functions. To achieve this goal, cell phenotype experiments, RNA sequencing (RNA-seq), and improved RNA immunoprecipitation sequencing (iRIP-seq) were conducted to identify the function and regulated targets of DEK in HeLa cells. The results showed DEK overexpression promoted cell proliferation and invasion of HeLa cells. Meanwhile, DEK hardly affected transcript level expression of those high expressed genes, but splicing pattern of 411 genes was regulated by DEK in HeLa cells, which were enriched in Hippo signaling pathway. Moreover, DEK broadly bind the RNA of a total of 11, 112 genes, with a biased binding the 5' splice site (5'SS) consensus GGUAA motifs at the CDS and intronic regions. In addition, 297 DEK-binding genes showed different splicing pattern after DEK overexpression in HeLa cells. These genes were enriched in Hippo signaling pathway including CSNK1D. The RT-qPCR and RIP-PCR confirmed that DEK can bind to CSNK1D to regulate its alternative splicing in HeLa cells. In summary, our results indicated DEK could broadly bind and regulate the pre-mRNA splicing process, which provide new insights of mechanisms that DEK functions in various biological processes including cancer.
| S-EPMC11903584 | biostudies-literature
Project description:Purpose: Explore how DEK genome widely bind RNA and affect the alternative splicing in cancer Methods: DEK was overexpressed by transfecting HeLa cells with a DEK-overexpressing plasmid and RNA_seq was used to analyze gene expression profile and splicing pattern of DEK overexpression and control cells. Then, an improved RIP-seq was conducted to explore genome-widely binding characteristic of DEK in HeLa cell. Bioinformatics analysis and qPCR/RIP-PCR were performed to identify and validate the bound and regulated targets of DEK, respectively Results:The results showed DEK overexpression did not affect transcript level expression of those high expressed genes (with FPKM > 1), but splicing pattern of 411 genes (RASGs) was regulated by DEK in HeLa cells, which were enriched in Hippo signaling pathway. Moreover, DEK broadly bind the RNA of a total of 11, 112 genes, with a biased binding the GGUAA motifs at the CDS and intronic regions Conclusions: our results indicated DEK could broadly bind and regulate the pre-mRNA splicing process, which provide new insights of mechanisms that DEK functions in various biological processes including cancer
2025-03-19 | GSE141566 | GEO
Project description:Purpose: Explore how DEK genome widely bind RNA and affect the alternative splicing in cancer Methods: DEK was overexpressed by transfecting HeLa cells with a DEK-overexpressing plasmid and RNA_seq was used to analyze gene expression profile and splicing pattern of DEK overexpression and control cells. Then, an improved RIP-seq was conducted to explore genome-widely binding characteristic of DEK in HeLa cell. Bioinformatics analysis and qPCR/RIP-PCR were performed to identify and validate the bound and regulated targets of DEK, respectively Results:The results showed DEK overexpression did not affect transcript level expression of those high expressed genes (with FPKM > 1), but splicing pattern of 411 genes (RASGs) was regulated by DEK in HeLa cells, which were enriched in Hippo signaling pathway. Moreover, DEK broadly bind the RNA of a total of 11, 112 genes, with a biased binding the GGUAA motifs at the CDS and intronic regions Conclusions: our results indicated DEK could broadly bind and regulate the pre-mRNA splicing process, which provide new insights of mechanisms that DEK functions in various biological processes including cancer
2025-03-19 | GSE141565 | GEO
Project description:DEK binds to pre-mRNAs and regulated alternative splicing of Hippo signaling genes in HeLa cell
| PRJNA593970 | ENA
Project description:DEK binds to pre-mRNAs and regulated alternative splicing of Hippo signaling genes in HeLa cell [RIP-seq]
| PRJNA593975 | ENA
Project description:DEK binds to pre-mRNAs and regulated alternative splicing of Hippo signaling genes in HeLa cell [RNA-seq]
| PRJNA593976 | ENA
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:Calcium homeostasis endoplasmic reticulum protein (CHERP) is colocalized with the inositol 1,4,5-trisphosphate receptor (IP3R) in the endoplasmic reticulum or perinuclear region, and has been involved in intracellular calcium signaling. Structurally, CHERP carries the nuclear localization signal and arginine/serine-dipeptide repeats, like domain, and interacts with the spliceosome. However, the exact function of CHERP in the nucleus remains unknown. Here, we showed that poly(A)+ RNAs accumulated in the nucleus of CHERP-depleted U2OS cells. Our global analysis revealed that CHERP regulated alternative mRNA splicing events by interaction with U2 small nuclear ribonucleoproteins (U2 snRNPs) and U2 snRNP-related proteins. Among the five alternative splicing patterns analyzed, intron retention was the most frequently observed event. This was in accordance with the accumulation of poly(A)+ RNAs in the nucleus. Furthermore, intron retention and cassette exon choices were influenced by the strength of the 5' or 3' splice site, the branch point site, GC content, and intron length. In addition, CHERP depletion induced anomalies in the cell cycle progression into the M phase, and abnormal cell division. These results suggested that CHERP is involved in the regulation of alternative splicing.
| S-EPMC8910253 | biostudies-literature
Project description:During liver regeneration, most new hepatocytes arise via self-duplication; yet, the underlying mechanisms that drive hepatocyte proliferation following injury remain poorly defined. By combining high-resolution transcriptome and polysome profiling of hepatocytes purified from quiescent and toxin-injured mouse livers, we uncover pervasive alterations in messenger RNA translation of metabolic and RNA-processing factors, which modulate the protein levels of a set of splicing regulators. Specifically, downregulation of the splicing regulator ESRP2 activates a neonatal alternative splicing program that rewires the Hippo signaling pathway in regenerating hepatocytes. We show that production of neonatal splice isoforms attenuates Hippo signaling, enables greater transcriptional activation of downstream target genes, and facilitates liver regeneration. We further demonstrate that ESRP2 deletion in mice causes excessive hepatocyte proliferation upon injury, whereas forced expression of ESRP2 inhibits proliferation by suppressing the expression of neonatal Hippo pathway isoforms. Thus, our findings reveal an alternative splicing axis that supports regeneration following chronic liver injury.
| S-EPMC6173981 | biostudies-literature
Project description:Alternative splicing (AS) is pervasive in human multi-exon genes and is a major contributor to expansion of the transcriptome and proteome diversity. The accurate recognition of alternative splice sites is regulated by information contained in networks of protein-protein and protein-RNA interactions. However, the mechanisms leading to splice site selection are not fully understood. Although numerous databases have been built to describe AS, molecular interaction databases associated with AS have only recently emerged. In this study, we present a new database, MiasDB, that provides a description of molecular interactions associated with human AS events. This database covers 938 interactions between human splicing factors, RNA elements, transcription factors, kinases and modified histones for 173 human AS events. Every entry includes the interaction partners, interaction type, experimental methods, AS type, tissue specificity or disease-relevant information, a simple description of the functionally tested interaction in the AS event and references. The database can be queried easily using a web server (http://47.88.84.236/Miasdb). We display some interaction figures for several genes. With this database, users can view the regulation network describing AS events for 12 given genes.
| S-EPMC4864242 | biostudies-literature