|
| Status |
Public on May 17, 2016 |
| Title |
Pervasive TTP binding but selective target mRNA destabilization in the macrophage transcriptome [RNA-Seq_2] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Other
|
| Summary |
Precise control of mRNA decay is fundamental for robust yet not exaggerated inflammatory responses to pathogens. Parameters determining the specificity and extent of mRNA degradation within the entire inflammation-associated transcriptome remain incompletely understood. Using transcriptome-wide high resolution occupancy assessment of the mRNA-destabilizing protein TTP, a major inflammation-limiting factor, we qualitatively and quantitatively characterize TTP binding positions and functionally relate them to TTP-dependent mRNA decay in immunostimulated macrophages. We identify pervasive TTP binding with incompletely penetrant linkage to mRNA destabilization. A necessary but not sufficient feature of TTP-mediated mRNA destabilization is binding to 3’ untranslated regions (UTRs). Mapping of binding positions of the mRNA-stabilizing protein HuR in activated macrophages revealed that TTP and HuR binding sites in 3’ UTRs occur mostly in different transcripts implicating only a limited co-regulation of inflammatory mRNAs by these proteins. Remarkably, we identify robust and widespread TTP binding to introns of stable transcripts. Nuclear TTP is associated with spliced-out introns and maintained in the nucleus throughout the inflammatory response. Our study establishes a functional annotation of binding positions dictating TTP-dependent mRNA decay in immunostimulated macrophages. The findings allow navigating the transcriptome-wide landscape of RNA elements controlling inflammation.
|
| |
|
| Overall design |
Experiment comparing RNA decay rates in WT and TTP-/- macrophages at LPS 3 h and 6 h. Transcription was blocked with actinomycin D for 0, 45 or 90 min. Decay rates was calculated using linear model.
|
| |
|
| Contributor(s) |
Sedlyarov V, Fallmann J, Ebner F, Ivin M, Kreiner K, Tanzer A, Hofacker I, Kovarik P |
| Citation(s) |
27178967 |
| Submission date |
Feb 23, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Vitaly Sedlyarov |
| Phone |
+4314016070050
|
| Organization name |
Research Center for Molecular Medicine
|
| Lab |
Prof. Giulio Superti-Furga
|
| Street address |
Lazarettgasse 14, AKH BT 25.3
|
| City |
Vienna |
| ZIP/Postal code |
1090 |
| Country |
Austria |
| |
|
| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
|
| Samples (42)
|
|
| This SubSeries is part of SuperSeries: |
| GSE63468 |
TTP binding site atlas in the macrophage transcriptome reveals a switch for inflammation resolution |
|
| Relations |
| BioProject |
PRJNA312931 |
| SRA |
SRP070703 |
Less...
More...