Genetic interactions and transcriptomics implicate fission yeast CTD prolyl isomerase Pin1 as an agent of RNA 3' processing and transcription termination that functions via its effects on CTD phosphatase Ssu72
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ABSTRACT:
PROVIDER: PRJNA602734 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10953369_1.fastq.gz | Fastqsanger.gz | |||
| SRR10953369_2.fastq.gz | Fastqsanger.gz | |||
| SRR10953370_1.fastq.gz | Fastqsanger.gz | |||
| SRR10953370_2.fastq.gz | Fastqsanger.gz | |||
| SRR10953371_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:This RNA-Seq analysis compares gene expression of the peptidyl-prolyl isomerase Pin1 mutant pin1∆ contrasting to the WT in the fission yeast S. pombe
2020-03-20 | GSE144092 | GEO
Project description:Genome-wide studies have identified abundant small, non-coding RNAs including snRNAs, snoRNAs, cryptic unstable transcripts (CUTs), and upstream regulatory RNAs (uRNAs) that are transcribed by RNA polymerase II (pol II) and terminated by a Nrd1-dependent pathway. Here, we show that the prolyl isomerase, Ess1, is required for Nrd1-dependent termination of ncRNAs. Ess1 binds the carboxy terminal domain (CTD) of pol II and is thought to regulate transcription by conformational isomerization of Ser-Pro bonds within the CTD. In ess1 mutants, expression of ~10% of the genome was altered, due primarily to defects in termination of snoRNAs, CUTs, SUTs and uRNAs. Ess1 promoted dephosphorylation of Ser5 (but not Ser2) within the CTD, most likely by the Ssu72 phosphatase, and we provide evidence for a competition between Nrd1 and Pcf11 for CTD-binding that is regulated by Ess1-dependent isomerization. This is the first example of a prolyl isomerase required for interpreting the “CTD code.”
2009-10-16 | GSE17638 | GEO
Project description:Mammalian cells possess intrinsic mechanisms to prevent tumorigenesis upon deleterious mutations, including oncogene-induced senescence (OIS). The molecular mechanisms underlying OIS are, however, complex, and remain to be characterized. In this study, we analyzed the changes in the nuclear (phospho)proteome during the progression of OIS. Interestingly, we found that most of the phosphosites regulated during OIS were Prolyl Isomerase Pin1 targets. Our results show that Pin1 is a key regulator of several PML-NB proteins, specifically regulating several proteins upon oncogene activation. We have found that the constitutive PML-NB proteins are significantly regulated when PIN1 is depleted. Furthermore, we show that PIN1 knockdown promotes cell proliferation, while diminishing the senescence phenotype and hallmarks of senescence such as p21. Thus, our data provides preliminary evidence that PML-NB proteins are involved in regulating OIS via phosphorylation, and that the prolyl isomerase PIN1 acts as a tumor suppressor in response to oncogenic ER:RasG12V activation.
| MSV000090326 | MassIVE
Project description:The prolyl isomerase PIN1 has been identified as a regulator of phosphorylation signalling that catalyses the conversion of specific phosphorylated motifs between the two completely distinct conformations in a subset of proteins. PIN1 regulates diverse cellular processes, including growth-signal responses, cell-cycle progression, cellular stress responses, neuronal function and immune responses. We used microarrays to detail the global gene expression of mammary epithelial cells (MECs) and neuron cells (NCs) in Pin1 KO and WT mice
2015-03-26 | GSE49971 | GEO
Project description:Pin1 is a prolyl isomerase that plays an important role in cancer, Alzheimer's disease, and asthma. To understand how Pin1 levels affect mRNA abundance on a genome-wide scale, we knocked down Pin1 by siRNA and used microarray-based gene expression profiling to identify candidate genes that are significantly up- or down-regulated by Pin1 siRNA. The data provide important information on Pin1-responsive genes. We find that genes that are inherently unstable and have short half-lives are targeted by Pin1.
2012-10-27 | GSE41868 | GEO
Project description:Transcription by RNA polymerase II (RNAPII) is coupled to mRNA processing and chromatin modifications via the C-terminal domain (CTD) of its largest subunit, consisting of multiple repeats of the heptapeptide YSPTSPS. Pioneering studies showed that CTD serines are differentially phosphorylated along genes in a prescribed pattern during the transcription cycle. Genome-wide analyses challenged this idea, suggesting that this cycle is non-uniform among different genes. Moreover, the respective role of enzymes responsible for CTD modifications remains controversial. Here, we systematically profiled the location of the RNAPII phospho-isoforms in wild type cells and mutants for most CTD modifying enzymes. Together with results of in vitro assays, these data reveal a complex interplay between the modifying enzymes, and provide evidence that the CTD cycle is uniform across genes. We also identify Ssu72 as the Ser7 phosphatase and show that proline isomerization is a key regulator of CTD dephosphorylation at the end of genes. We took a systematic approach to examine the genome-wide distribution of the various CTD modifications using a panel of RNAPII CTD phospho-specific antibodies; both in wild type cells and in mutants for most of the CTD kinases, phosphatases and the isomerase. Immunoprecipitation of CTD phospho-isoforms were done using the following antibodies: H14 and 3E8 for Ser5, H5 and 3E10 for Ser2, 4E12 for Ser7, 8WG16 (anti-Rpb1-CTD) and W0012 (anti-Rpb3) for RNAPII (global localization). A list of the mutant strains and their genotypes can be found in the supplemental files of the related publication. Most ChIPs (in Cy5) were hybridyzed against a non-immunoprecipitated (whole cell extract, WCE) in Cy3. Ssu72, Pti1 and Rpb1 were immunoprecipitated using tagged proteins (3myc-Ssu72, Pti1-3myc, Rpb1-9myc) and the ChIP DNA hybridized in competition with a control ChIP DNA prepared from an isogenic untagged strain (NoTag). ChIP from wild type strains yFR116 (W303) and yFR117 (S288C) were used to obtains wild type profiles that can be compared to mutants strains of the same background. All ChIP-chip experiments were done at least in duplicates. Each microarray was normalized using the Lima Loess and replicates were combined using a weighted average method as previously described (Pokholok et al., 2005).
2012-02-01 | E-GEOD-29403 | biostudies-arrayexpress
Project description:Pin1 is a prolyl isomerase that plays an important role in cancer, Alzheimer's disease, and asthma. To understand how Pin1 levels affect mRNA abundance on a genome-wide scale, we knocked down Pin1 by siRNA and used microarray-based gene expression profiling to identify candidate genes that are significantly up- or down-regulated by Pin1 siRNA. The data provide important information on Pin1-responsive genes. We find that genes that are inherently unstable and have short half-lives are targeted by Pin1. Total RNA was obtained from HeLa cells treated with either control siRNA or an siRNA towards Pin1. There were three replicates each for the control and the siRNA-treated cells. The average signal for the three replicates is reported.
2012-10-27 | E-GEOD-41868 | biostudies-arrayexpress
Project description:Bladder cancer, one of the most diagnosed cancers worldwide, is associated with high morbidity, mortality, and a poor prognosis. The PIN1 phospho-dependent prolyl isomerase is frequently overexpressed in many human cancer types and affects tumor initiation and progression through disrupting the balance of oncoprotein and tumor suppressor protein signaling. However, the functional pSer/Thr.Pro protein substrates of PIN1 and its effects on downstream signaling in bladder carcinogenesis remain largely unknown. Phenotypically, we discovered that ablation of Pin1 in human/mouse bladder cancer cells and organoids formed from mouse primary urothelial cells resulted in decreased cell proliferation, stemness maintenance, cell invasion, migration, urothelium clearance capacity, and reduced free/total cholesterol levels in vitro. Re-expressing Pin1 in Pin1 knockout cells reversed the defects caused by lack of Pin1. Moreover, in vivo subcutaneous xenograft and allograft transplantation mouse models combined with an orthotopic implantation model were utilized to confirm a positive role for Pin1 in controlling tumor growth and potential metastasis. Therapeutically, a combination of the sulfopin PIN1 inhibitor and the simvastatin HMGCR inhibitor was shown to suppress cell proliferation in vitro and tumor growth in vivo synergistically. Mechanistically, we observed a negative enrichment of SREBP2-driven cholesterol metabolism pathways in PIN1 knockout cells via RNA-sequencing and used a suite of diverse molecular and biochemical approaches to show that PIN1 interacts with JNK-dependent phosphorylated SREBP2 (Ser455) and vice versa. These results indicate that active cholesterol biosynthesis pathway in bladder cancer cells is regulated by PIN1-mediated isomerization and JNK-mediated phosphorylation of its key transcriptional factor SREBP2. These findings emphasize that PIN1 can act as a regulator and potential therapeutic target in bladder cancer.
2024-11-17 | GSE262761 | GEO
Project description:The c-myc proto-oncogene is activated by translocation in Burkitt's lymphoma and substitutions in codon 58 stabilize the Myc protein or augment its oncogenic potential. In wild-type Myc, phosphorylation of Ser 62 and Thr 58 provide a landing pad for the peptidyl prolyl-isomerase Pin1, which in turn promotes Ser 62 dephosphorylation and Myc degradation. However, the role of Pin1 in Myc-induced lymphomagenesis remains unknown. We show here that genetic ablation of Pin1 reduces lymphomagenesis in Eµ-myc transgenic mice. In both Pin1-deficient B-cells and MEFs, the proliferative response to Myc was selectively impaired, with no alterations in Myc-induced apoptosis or mitogen-induced cell cycle entry. This proliferative defect wasn't attributable to alterations in either Ser 62 phosphorylation or Myc-regulated transcription, but to the indirect activation of an Arf-p53 dependent cytostatic response. Pin1 silencing in lymphomas retarded disease progression in mice, making Pin1 an attractive therapeutic target in Myc-driven tumors. RNAseq samples of Pin1+/+ control (n=4), Pin1 -/- control (n=2), Pin1+/+ Eµ-myc pre-tumoral (n=3), and Pin1-/- Eµ-myc pre-tumoral (n=4) B cells.
2016-06-14 | E-GEOD-77482 | biostudies-arrayexpress
Project description:The peptidyl-prolyl isomerase, Pin1, is exploited in cancer to activate oncogenes and inactivate tumor suppressors. However, despite considerable efforts, Pin1 has remained an elusive drug target. Here, we screened an electrophilic fragment library to identify covalent inhibitors targeting Pin1’s active site Cys113, leading to the development of Sulfopin, a nanomolar Pin1 inhibitor. Sulfopin is highly selective, as validated by two independent chemoproteomics methods, achieves potent cellular and in vivo target engagement, and phenocopies Pin1 genetic knockout. Pin1 inhibition had only a modest effect on cancer cell line viability. Still, Sulfopin induced downregulation of c-Myc target genes, reduced tumor progression and conferred survival benefit in murine and zebrafish models of MYCN-driven neuroblastoma, and in a murine model of pancreatic cancer. Our results demonstrate that Sulfopin is a suitable chemical probe for assessing Pin1-dependent pharmacology in cells and in vivo, and that Pin1 warrants further investigation as a potential cancer drug target.
2021-04-01 | GSE166786 | GEO