Tiedje et al. 2016 (PRJNA321057)
General Details
| Title | The RNA-binding protein TTP is a global post-transcriptional regulator of feedback control in inflammation [Ribo-seq] |
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| Organism | |
| Number of Samples | 9 |
| Release Date | 2016/05/09 00:00 |
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| Protocol Details |
Study Links
| GWIPS-viz | Trips-Viz |
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Repository Details
| SRA | SRP074604 |
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| ENA | SRP074604 |
| GEO | GSE81247 |
| BioProject | PRJNA321057 |
Publication
| Title | |
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| Authors | Tiedje C,Diaz-Muñoz MD,Trulley P,Ahlfors H,Laaß K,Blackshear PJ,Turner M,Gaestel M |
| Journal | Nucleic acids research |
| Publication Date | 2016 Sep 6 |
| Abstract | RNA-binding proteins (RBPs) facilitate post-transcriptional control of eukaryotic gene expression at multiple levels. The RBP tristetraprolin (TTP/Zfp36) is a signal-induced phosphorylated anti-inflammatory protein guiding unstable mRNAs of pro-inflammatory proteins for degradation and preventing translation. Using iCLIP, we have identified numerous mRNA targets bound by wild-type TTP and by a non-MK2-phosphorylatable TTP mutant (TTP-AA) in 1 h LPS-stimulated macrophages and correlated their interaction with TTP to changes at the level of mRNA abundance and translation in a transcriptome-wide manner. The close similarity of the transcriptomes of TTP-deficient and TTP-expressing macrophages upon short LPS stimulation suggested an effective inactivation of TTP by MK2, whereas retained RNA-binding capacity of TTP-AA to 3'UTRs caused profound changes in the transcriptome and translatome, altered NF-κB-activation and induced cell death. Increased TTP binding to the 3'UTR of feedback inhibitor mRNAs, such as Ier3, Dusp1 or Tnfaip3, in the absence of MK2-dependent TTP neutralization resulted in a strong reduction of their protein synthesis contributing to the deregulation of the NF-κB-signaling pathway. Taken together, our study uncovers a role of TTP as a suppressor of feedback inhibitors of inflammation and highlights the importance of fine-tuned TTP activity-regulation by MK2 in order to control the pro-inflammatory response. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. |
| PMC | PMC5009735 |
| PMID | 27220464 |
| DOI |
| Run Accession | Study Accession | Scientific Name | Cell Line | Library Type | Treatment | GWIPS-viz | Trips-Viz | Reads | BAM | BigWig (F) | BigWig (R) | ||
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| SRR3488640 | PRJNA321057 | Mus musculus | bone marrow-derived macrophages (BMDMs)_immortalized primary cells | Ribo-Seq |  |
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| SRR3488641 | PRJNA321057 | Mus musculus | bone marrow-derived macrophages (BMDMs)_immortalized primary cells | Ribo-Seq | |
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| SRR3488642 | PRJNA321057 | Mus musculus | bone marrow-derived macrophages (BMDMs)_immortalized primary cells | Ribo-Seq | |
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| SRR3488643 | PRJNA321057 | Mus musculus | bone marrow-derived macrophages (BMDMs)_immortalized primary cells | Ribo-Seq | |
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| SRR3488644 | PRJNA321057 | Mus musculus | bone marrow-derived macrophages (BMDMs)_immortalized primary cells | Ribo-Seq | |
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| SRR3488645 | PRJNA321057 | Mus musculus | bone marrow-derived macrophages (BMDMs)_immortalized primary cells | Ribo-Seq | |
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| SRR3488646 | PRJNA321057 | Mus musculus | bone marrow-derived macrophages (BMDMs)_immortalized primary cells | Ribo-Seq | |
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| SRR3488647 | PRJNA321057 | Mus musculus | bone marrow-derived macrophages (BMDMs)_immortalized primary cells | Ribo-Seq | |
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| SRR3488648 | PRJNA321057 | Mus musculus | bone marrow-derived macrophages (BMDMs)_immortalized primary cells | Ribo-Seq | |
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| Run Accession | Study Accession | Scientific Name | Cell Line | Library Type | Treatment | GWIPS-viz | Trips-Viz | Reads | BAM | BigWig (F) | BigWig (R) |
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