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| 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
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| 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.
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| 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.
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| Contributor(s) |
Chang X, Wang Z |
| Citation(s) |
29958803 |
| |
| Submission date |
Jul 21, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Xing Chang |
| E-mail(s) |
changxing@sibs.ac.cn
|
| Organization name |
Shanghai Institute for Biological Sciences
|
| Street address |
320 Yueyang road
|
| City |
Shanghai |
| ZIP/Postal code |
200031 |
| Country |
China |
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| Platforms (2) |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE84702 |
Iron-mediated stabilization of PCBP1 post-transcriptionally promotes GM-CSF production during autoimmune pathogenesis |
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| Relations |
| BioProject |
PRJNA330856 |
| SRA |
SRP079236 |
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