SNRPB knockdown in GBM
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB10298 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR1414340_1.fastq.gz | Fastqsanger.gz | |||
| ERR1414340_2.fastq.gz | Fastqsanger.gz | |||
| ERR1414341_1.fastq.gz | Fastqsanger.gz | |||
| ERR1414341_2.fastq.gz | Fastqsanger.gz | |||
| ERR1414342_1.fastq.gz | Fastqsanger.gz |
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Project description:Dysregulated alternative splicing has been closely linked to the initiation and progression of tumors. Nevertheless, the precise molecular mechanisms through which splicing factors regulate endometrial cancer progression are still not fully understood. This study demonstrated the elevated expression of the splicing factor SNRPB in endometrial cancer samples. Furthermore, our findings indicated that high levels of SNRPB expression are correlated with a poor prognosis in endometrial cancer patients. Functionally, SNRPB inhibition hindered proliferative and metastatic capacities of endometrial cancer cells. Mechanistically, we revealed that SNRPB knockdown decreased POLD1 expression, and there was retention of POLD1 intron 22 after SNRPB silencing in endometrial cancer cells based on RNA-seq data analysis. The retained intron 22 of POLD1 created a premature termination codon, leading to the absence of amino acids 941 to 1107 and loss of the site of interaction with PCNA, which is essential for POLD1 enzyme activity. In addition, POLD1 depletion decreased the increase in the malignancy of endometrial cancer cells overexpressing SNRPB. Furthermore, miR-654-5p was found to bind to the 3’-UTR of SNRPB directly, resulting in SNRPB expression inhibition in endometrial cancer. Antisense oligonucleotide-mediated SNRPB inhibition led to a decrease in the growth capacity of a CDX model and a PDX model. Overall, SNRPB promotes the efficient splicing of POLD1 by regulating intron retention, ultimately contributing to high POLD1 expression in endometrial cancer. The oncogenic SNRPB/POLD1 axis is an interesting therapeutic target for endometrial cancer, and ASO-mediated silencing of SNRPB may offer a promising therapeutic approach for treating endometrial cancer patients.
2025-03-12 | GSE279656 | GEO
Project description:RNA sequencing of SNRPA1 and SNRPB knockdown in MDA-LM2 cells
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Project description:Purpose: Heterozygous mutations in SNRPB, an essential core component of the five small ribonucleoprotein particles of the spliceosome, are responsible for craniofacial and rib defects in patients with Cerebrocostomandibular Syndrome (CCMS). However, why the mutations in SNRPB causes tissue specific CCMS abnormalities such as craniofacial defects are unknown. We hypothesize that splicing of tissue specific transcripts required for craniofacial development is disrupted due to SNRPB deficiency, during embryonic development. The purpose of the study was to identify those developmentally important transcripts that are dysregulated due to Snrpb mutation. Methods: We mated Snrpbloxp mice that we have developed with commercially available Wnt-1-Cre2 transgenic mice to remove one allele of Snrpb from neural crest cells. The mutant (Snrpb \ncc+/-) embryos showed craniofacial abnormalities at E9.5 and onward. We collected morphologically normal embryos at E9.0 for both Snrpb wildtype and Snrpbncc+/- mutants. We pooled two embryo heads of similar somites for each genotype and extracted the RNA for RNAseq. Results: We found that Snrpbncc+/- mutants show aberrant splicing that includes both increased exon skipping and intron retention. A strong tendency towards increased exon skipping and intron inclusion in the mutant samples were observed; there were more SE (273 in Het versus 83 in WT) and RI (191 in Het versus 21 in WT). We identified 13 transcripts required for craniofacial development or stem cell development with significant increases in exon skipping including Smad2, Rere and Pou2f1. From pathway analysis of differentially expressed genes, we found they were associated with the spliceosome and the P53-pathway. We also found an increase in splicing of two P53 regulator, Mdm2 and Mdm4. Conclusions: We propose that abnormal splicing underlies the defects found in Snrpbncc+/-mutant embryos. We confirmed differential splicing of the P53 regulators, Mdm2 and Mdm4 and identified several transcripts important for craniofacial development which were abnormally spliced in Snrpbncc+/- embryos.
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Project description:Detection of transcriptome changes caused by knockdown of Ptbp1 in U251 GBM cells
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Project description:Protein Arginine Methyltransferase 5 (PRMT5) regulates RNA splicing and transcription by symmetric dimethylation of arginine residues (Rme2s/SDMA) in many RNA binding proteins. However, the mechanism by which PRMT5 couples splicing to transcriptional output is unknown. Here, we demonstrate that a major function of PRMT5 activity is to promote chromatin escape of a novel, large class of mRNAs that we term Genomically Retained Incompletely Processed Polyadenylated Transcripts (GRIPPs). Using nascent and total transcriptomics, spike-in controlled fractionated cell transcriptomics, and total and fractionated cell proteomics, we show that PRMT5 inhibition and knockdown of the PRMT5 SNRP (Sm protein) adapter protein pICln (CLNS1A) —but not type I PRMT inhibition—leads to gross detention of mRNA, SNRPB, and SNRPD3 proteins on chromatin. Compared to most transcripts, these chromatin-trapped polyadenylated RNA transcripts have more introns, are spliced slower, and are enriched in detained introns. Using a combination of PRMT5 inhibition and inducible isogenic wildtype and arginine-mutant SNRPB, we show that arginine methylation of these snRNPs is critical for mediating their homeostatic chromatin and RNA interactions. Overall, we conclude that a major role for PRMT5 is in controlling transcript processing and splicing completion to promote chromatin escape and subsequent nuclear export.
2025-09-01 | GSE275215 | GEO
Project description:We demonstrated that knocking down Ptbp1 can reprogram GBM cells into neuron-like cells. In order to further explore the mechanism of Ptbp1 causing this phenomenon, we performed mRNA sequencing on U251 cells infected with sh-Luci-3d, sh-Ptbp1-3d and sh-Ptbp1-7d.
2022-06-01 | GSE189816 | GEO
Project description:Glioma is a malignant primary tumour that occurs in the central nervous system. TEA domain transcription factor (TEAD) family proteins are the Hippo pathway's ultimate effector molecules. The function of TEAD3 in gliomas is still unclear. Therefore, RNA sequencing was performed on TEAD3 knockdown U251 cells and normal U251 cells. The samples in this study included normal U251 control group and TEAD3 knockdown group. Each group contained three samples. Total RNA was extracted using Trizol reagent following the manufacturer's procedure. The total RNA quantity and purity were analysis of Bioanalyzer 2100 and RNA 6000 Nano LabChip Kit, high-quality RNA samples with RIN number > 7.0 were used to construct sequencing library. Gene Set Enrichment Analysis (GSEA) based on the sequencing results showed that knockdown of TEAD3 in the U251 cell line caused changes in several important pathways, including CTLA4 inhibitory pathway, defective pyroptosis, signaling by Hippo, regulation of TP53 activity, E2F mediated regulation of DNA replication, and FCGR3A mediated phagocytosis.
2023-01-25 | GSE223378 | GEO
Project description:Protein Arginine Methyltransferase 5 (PRMT5) regulates RNA splicing and transcription by symmetric dimethylation of arginine residues (Rme2s/SDMA) in many RNA binding proteins. However, the mechanism by which PRMT5 couples splicing to transcriptional output is unknown. Here, we demonstrate that a major function of PRMT5 activity is to promote chromatin escape of a novel, large class of mRNAs that we term Genomically Retained Incompletely Processed Polyadenylated Transcripts (GRIPPs). Using nascent and total transcriptomics, spike-in controlled fractionated cell transcriptomics, and total and fractionated cell proteomics, we show that PRMT5 inhibition and knockdown of the PRMT5 SNRP (Sm protein) adapter protein pICln (CLNS1A) —but not type I PRMT inhibition—leads to gross detention of mRNA, SNRPB, and SNRPD3 proteins on chromatin. Compared to most transcripts, these chromatin-trapped polyadenylated RNA transcripts have more introns, are spliced slower, and are enriched in detained introns. Using a combination of PRMT5 inhibition and inducible isogenic wildtype and arginine-mutant SNRPB, we show that arginine methylation of these snRNPs is critical for mediating their homeostatic chromatin and RNA interactions. Overall, we conclude that a major role for PRMT5 is in controlling transcript processing and splicing completion to promote chromatin escape and subsequent nuclear export.
2025-10-06 | GSE275217 | GEO
Project description:Protein Arginine Methyltransferase 5 (PRMT5) regulates RNA splicing and transcription by symmetric dimethylation of arginine residues (Rme2s/SDMA) in many RNA binding proteins. However, the mechanism by which PRMT5 couples splicing to transcriptional output is unknown. Here, we demonstrate that a major function of PRMT5 activity is to promote chromatin escape of a novel, large class of mRNAs that we term Genomically Retained Incompletely Processed Polyadenylated Transcripts (GRIPPs). Using nascent and total transcriptomics, spike-in controlled fractionated cell transcriptomics, and total and fractionated cell proteomics, we show that PRMT5 inhibition and knockdown of the PRMT5 SNRP (Sm protein) adapter protein pICln (CLNS1A) —but not type I PRMT inhibition—leads to gross detention of mRNA, SNRPB, and SNRPD3 proteins on chromatin. Compared to most transcripts, these chromatin-trapped polyadenylated RNA transcripts have more introns, are spliced slower, and are enriched in detained introns. Using a combination of PRMT5 inhibition and inducible isogenic wildtype and arginine-mutant SNRPB, we show that arginine methylation of these snRNPs is critical for mediating their homeostatic chromatin and RNA interactions. Overall, we conclude that a major role for PRMT5 is in controlling transcript processing and splicing completion to promote chromatin escape and subsequent nuclear export.
2025-09-01 | GSE275214 | GEO
Project description:Protein Arginine Methyltransferase 5 (PRMT5) regulates RNA splicing and transcription by symmetric dimethylation of arginine residues (Rme2s/SDMA) in many RNA binding proteins. However, the mechanism by which PRMT5 couples splicing to transcriptional output is unknown. Here, we demonstrate that a major function of PRMT5 activity is to promote chromatin escape of a novel, large class of mRNAs that we term Genomically Retained Incompletely Processed Polyadenylated Transcripts (GRIPPs). Using nascent and total transcriptomics, spike-in controlled fractionated cell transcriptomics, and total and fractionated cell proteomics, we show that PRMT5 inhibition and knockdown of the PRMT5 SNRP (Sm protein) adapter protein pICln (CLNS1A) —but not type I PRMT inhibition—leads to gross detention of mRNA, SNRPB, and SNRPD3 proteins on chromatin. Compared to most transcripts, these chromatin-trapped polyadenylated RNA transcripts have more introns, are spliced slower, and are enriched in detained introns. Using a combination of PRMT5 inhibition and inducible isogenic wildtype and arginine-mutant SNRPB, we show that arginine methylation of these snRNPs is critical for mediating their homeostatic chromatin and RNA interactions. Overall, we conclude that a major role for PRMT5 is in controlling transcript processing and splicing completion to promote chromatin escape and subsequent nuclear export.
2025-10-06 | GSE275220 | GEO