PCBP1 regulates transcription by binding ssDNA at promoters
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE225637 | GEO | 2025/05/01
REPOSITORIES: GEO
Similar Datasets
Project description:PCBP1 regulates transcription by binding ssDNA at promoters
| PRJNA936868 | ENA
Project description:RNA-binding proteins participate in a complex array of post-transcriptional controls essential to cell-type specification and somatic development. Despite their detailed biochemical characterizations, the degree to which each RNA-binding protein impacts on mammalian embryonic development remains incompletely defined and the level of functional redundancy among subsets of these proteins remains open to question. The poly-(C) binding proteins, Pcbp's (aCPs, hnRNPEs), are encoded by a highly conserved and broadly expressed gene family. The two major Pcbp isoforms, Pcbp2 and Pcbp1, are robustly expressed in a wide range of tissues and exert both nuclear and cytoplasmic controls over gene expression. Here we report that Pcbp1-null embryos are rendered nonviable in the peri-implantation stage. In contrast, Pcbp2-null embryos survive until mid-gestation at which time they undergo a loss in viability associated with cardiovascular and hematopoietic abnormalities. Adult mice heterozygous for either Pcbp1 or Pcbp2 null alleles display a mild and non-disruptive growth defect. These data reveal that Pcbp1 and Pcbp2 are individually essential for mouse embryonic development and post-natal growth, reveal a non-redundant in vivo role for Pcpb2 in hematopoiesis, and provide direct evidence that Pcbp1, a retrotransposed derivative of Pcpb2, has evolved essential function(s) in the mammalian genome. mRNA-seq on fetal liver tissue from 12.5 days post coitum. 4 replicates of WT and 3 replicates of PCBP2 Knockout
2015-11-05 | E-GEOD-72491 | biostudies-arrayexpress
Project description:Iron deposition is frequently observed in human autoinflammatory diseases, such as in the brain of patients with multiple sclerosis or in the synovial fluid of patients with rheumatoid arthritis1-5. Yet, the functional outcome of excessive iron in inflammatory conditions is largely unknown. Granulocyte macrophage colony-stimulating factor (GM-CSF) is a proinflammatory cytokine promoting myeloid cell maturation and activation6 and is essential for the pathogenesis of many autoimmune diseases, including autoimmune encephalomyelitis7-10. Post-transcriptional regulation of GM-CSF is mediated primarily through its 3’ untranslated region (3’UTR) via interaction with specific RNA-binding proteins11. Here we show that a RNA-binding protein PCBP1 senses intracellular iron and post-transcriptionally promotes GM-CSF production. In a short hairpin (sh) RNA screening, we found that Poly(rC) binding protein 1 (PCBP1) enhanced GM-CSF 3’UTR activity and its endogenous mRNA stability. PCBP1 deficiency in autoreactive T cells resulted in a compromised production of GM-CSF and other proinflammatory cytokines, abolishing their capacity in inducing experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Using Crosslinking and Immunoprecipitation (CLIP)12, we demonstrated that PCBP1 promoted mRNA stability by recognizing CU rich elements in the 3’UTRs of pro-inflammatory cytokines. Furthermore, iron depletion induced rapid caspase-mediated proteolysis of PCBP1 and inhibited the production of GM-CSF and a module of 24 cytokines in primary murine and human T cells. Our study thus demonstrates that PCBP1 is critical for the post-transcriptional regulation of proinflammatory cytokines, and indicates that sensing iron may represent a simple yet effective means to adjust the inflammatory response to tissue homeostatic alterations.
2018-07-04 | GSE84699 | GEO
Project description:Iron deposition is frequently observed in human autoinflammatory diseases, such as in the brain of patients with multiple sclerosis or in the synovial fluid of patients with rheumatoid arthritis1-5. Yet, the functional outcome of excessive iron in inflammatory conditions is largely unknown. Granulocyte macrophage colony-stimulating factor (GM-CSF) is a proinflammatory cytokine promoting myeloid cell maturation and activation6 and is essential for the pathogenesis of many autoimmune diseases, including autoimmune encephalomyelitis7-10. Post-transcriptional regulation of GM-CSF is mediated primarily through its 3’ untranslated region (3’UTR) via interaction with specific RNA-binding proteins11. Here we show that a RNA-binding protein PCBP1 senses intracellular iron and post-transcriptionally promotes GM-CSF production. In a short hairpin (sh) RNA screening, we found that Poly(rC) binding protein 1 (PCBP1) enhanced GM-CSF 3’UTR activity and its endogenous mRNA stability. PCBP1 deficiency in autoreactive T cells resulted in a compromised production of GM-CSF and other proinflammatory cytokines, abolishing their capacity in inducing experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Using Crosslinking and Immunoprecipitation (CLIP)12, we demonstrated that PCBP1 promoted mRNA stability by recognizing CU rich elements in the 3’UTRs of pro-inflammatory cytokines. Furthermore, iron depletion induced rapid caspase-mediated proteolysis of PCBP1 and inhibited the production of GM-CSF and a module of 24 cytokines in primary murine and human T cells. Our study thus demonstrates that PCBP1 is critical for the post-transcriptional regulation of proinflammatory cytokines, and indicates that sensing iron may represent a simple yet effective means to adjust the inflammatory response to tissue homeostatic alterations.
2018-07-04 | GSE84700 | GEO
Project description:E14.5 fetal liver cells from CD-1 mice were enriched for hematopoietic progenitors. The purified hematopoietic progenitor cells were infected immediately with retroviruses encoding shRNAs that target Pcbp1, Pcbp2, as well as two sets of control shRNAs; Luciferase and scrambled sequence. The transduced cells were grown for 48 hours. These cells were collected (‘Day 0’ cells), or washed and resuspended in differentiation medium and incubated for an additional 2 days (‘Day 2’ cells). 1ug of total RNA isolated from ‘Day 0’ and ‘Day 2’ cells from each Pcbp1 or Pcbp2 depleted sample was used for cDNA library construction after polyA selection. A total of 9 samples were generated from each of the two time points: 3 controls; Pcbp1 knockdowns with three distinctly targeting shRNAs (sh1,3,4); Pcbp2 knockdown with three distinctly targeting shRNAs (sh1,3,4). Sequencing was carried out using a 150nt paired-end sequencing protocol.
2021-07-01 | GSE178247 | GEO
Project description:B cells are crucial for adaptive immunity, orchestrating humoral responses by producing antibodies essential for pathogen clearance. Here, we show that Poly(rC) binding protein 1 (Pcbp1), a multifunctional RNA-binding protein, is a key regulator of antibody production in B cells. Pcbp1 deficiency in B cells resulted in significant reductions in IgM expression at steady state and compromised differentiation of germinal center B cells and production of high-affinity antibodies upon immunization. These effects result from compromised mitochondrial integrity in Pcbp1-deficient B cells, including compromised mitochondrial electron transport chain (ETC) complex I and increased mitochondrial ROS production. Blocking mitochondrial ROS production rescued IgM production and improved germinal center responses caused by Pcbp1 deficiency. Mechanistically, Pcbp1 promotes the expression of Fdxr, a critical component of ETC complex I, via binding to its 3’UTR. Overall, our findings reveal a novel role for Pcbp1 in regulating mitochondrial function, protein synthesis, and antibody responses in B cells, providing novel insight into post-transcriptional regulation and mitochondrial functions.
2024-08-31 | GSE275672 | GEO
Project description:B cells are crucial for adaptive immunity, orchestrating humoral responses by producing antibodies essential for pathogen clearance. Here, we show that Poly(rC) binding protein 1 (Pcbp1), a multifunctional RNA-binding protein, is a key regulator of antibody production in B cells. Pcbp1 deficiency in B cells resulted in significant reductions in IgM expression at steady state and compromised differentiation of germinal center B cells and production of high-affinity antibodies upon immunization. These effects result from compromised mitochondrial integrity in Pcbp1-deficient B cells, including compromised mitochondrial electron transport chain (ETC) complex I and increased mitochondrial ROS production. Blocking mitochondrial ROS production rescued IgM production and improved germinal center responses caused by Pcbp1 deficiency. Mechanistically, Pcbp1 promotes the expression of Fdxr, a critical component of ETC complex I, via binding to its 3’UTR. Overall, our findings reveal a novel role for Pcbp1 in regulating mitochondrial function, protein synthesis, and antibody responses in B cells, providing novel insight into post-transcriptional regulation and mitochondrial functions.
2024-08-31 | GSE275669 | GEO
Project description:CUT&RUN to map ARID2 and BRG1 genomic associations in late prophase-I and metaphase-I spermatocytes
2021-10-11 | GSE167539 | GEO
Project description:Distinct lineages of T cells can act in response to various environmental cues to either drive or restrict immune-mediated pathology. Immunotherapy involving the block of cell surface immune checkpoints CTLA-4 and PD-1/PD-L1 has revolutionized cancer treatment across a wide spectrum of malignancies. However, additional immune regulatory mechanisms remain to be discovered, and will facilitate development of next generation agents to overcome resistance to current therapies. We now report that the RNA-binding protein, PCBP1, is critical for stabilizing effector T cell functions by limiting expression of T effector cell-intrinsic Treg-commitment programs and subverting expression of immune-suppressive signals. Indeed, T cell-specific deletion of Pcbp1 increased Treg development, enlisted multiple inhibitory checkpoint molecules including PD-1, TIGIT and VISTA on TILs, and thwarted anti-tumor immunity. Our results demonstrate a critical role for PCBP1 as an intracellular checkpoint for balancing effector versus Treg cells and also suggest PCBP1 as a novel target for cancer immunotherapy.
2020-06-16 | GSE131826 | GEO
Project description:RNA-binding proteins participate in a complex array of post-transcriptional controls essential to cell-type specification and somatic development. Despite their detailed biochemical characterizations, the degree to which each RNA-binding protein impacts on mammalian embryonic development remains incompletely defined and the level of functional redundancy among subsets of these proteins remains open to question. The poly-(C) binding proteins, Pcbp’s (aCPs, hnRNPEs), are encoded by a highly conserved and broadly expressed gene family. The two major Pcbp isoforms, Pcbp2 and Pcbp1, are robustly expressed in a wide range of tissues and exert both nuclear and cytoplasmic controls over gene expression. Here we report that Pcbp1-null embryos are rendered nonviable in the peri-implantation stage. In contrast, Pcbp2-null embryos survive until mid-gestation at which time they undergo a loss in viability associated with cardiovascular and hematopoietic abnormalities. Adult mice heterozygous for either Pcbp1 or Pcbp2 null alleles display a mild and non-disruptive growth defect. These data reveal that Pcbp1 and Pcbp2 are individually essential for mouse embryonic development and post-natal growth, reveal a non-redundant in vivo role for Pcpb2 in hematopoiesis, and provide direct evidence that Pcbp1, a retrotransposed derivative of Pcpb2, has evolved essential function(s) in the mammalian genome.
2015-11-05 | GSE72491 | GEO