GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE84699 Query DataSets for GSE84699
Status Public on Jul 04, 2018
Title Transcriptome targets of PCBP1 in T cells
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary 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.
Overall design We apply high-throughput RNA seq analysis to determine the transcriptome change in murine Th1 cells after either shRNA mediated knockdown of PCBP1 or depletion of intracellular iron by an iron chelator ciclopirox olamine.
Contributor(s) Chang X, Wang Z
Citation(s) 29958803
Submission date Jul 21, 2016
Last update date May 15, 2019
Contact name Xing Chang
Organization name Shanghai Institute for Biological Sciences
Street address 320 Yueyang road
City Shanghai
ZIP/Postal code 200031
Country China
Platforms (2)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
GPL21273 HiSeq X Ten (Mus musculus)
Samples (8)
GSM2247806 Ctrl Th1 cells Rep 1
GSM2247807 Ctrl Th1 cells Rep 2
GSM2247808 PCBP1 KD Th1 cells Rep 1
This SubSeries is part of SuperSeries:
GSE84702 Iron-mediated stabilization of PCBP1 post-transcriptionally promotes GM-CSF production during autoimmune pathogenesis
BioProject PRJNA330856
SRA SRP079236

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE84699_RNAseq_cpx_vs_dmso_DESeq2.txt.gz 675.9 Kb (ftp)(http) TXT
GSE84699_RNAseq_pcbp1kd_vs_control_DESeq2.txt.gz 687.6 Kb (ftp)(http) TXT
GSE84699_RPM.txt.gz 353.1 Kb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap