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Status |
Public on Jul 20, 2015 |
Title |
RC3H1 posttranscriptionally regulates A20 mRNA and modulates the activity of the IKK/NF-kB pathway [PARCLIP] |
Organism |
Homo sapiens |
Experiment type |
Non-coding RNA profiling by high throughput sequencing
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Summary |
The RNA-binding protein RC3H1 (also known as ROQUIN) promotes TNFalpha mRNA decay via a 3'UTR constitutive decay element (CDE). Here, we applied PAR-CLIP to human RC3H1 to identify about 3800 mRNA targets with more than 16000 binding sites. A large number of sites are distinct from the consensus CDE and revealed a structure-sequence motif with U-rich sequences embedded in hairpins. RC3H1 binds preferentially short-lived and DNA damage induced mRNAs, indicating a role of this RNA-binding protein in the posttranscriptional regulation of the DNA damage response. Intriguingly, RC3H1 affects expression of NF-kB pathway regulators such as IkBalpha and A20. RC3H1 uses roquin and Zn-finger domains to contact a binding site in the A20 3'UTR, demonstrating a not yet recognized mode of RC3H1 binding. Knockdown of RC3H1 resulted in increased A20 protein expression, thereby interfering with IkB kinase and NF-kB activities, demonstrating that RC3H1 can modulate the activity of the IKK/NF-kB pathway.
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Overall design |
One PAR-CLIP Sample with human HEK293 cells
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Contributor(s) |
Murakawa Y, Landthaler M |
Citation(s) |
26170170 |
Submission date |
May 18, 2013 |
Last update date |
May 15, 2019 |
Contact name |
Markus Landthaler |
E-mail(s) |
markus.landthaler@mdc-berlin.de
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Phone |
+49-30-9406-3026
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Organization name |
Max-Delbrück-Center for Molecular Medicine
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Department |
Berlin Institute for Medical Systems Biology
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Street address |
Robert-Rössle-Straße 10
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City |
Berlin |
ZIP/Postal code |
13125 |
Country |
Germany |
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Platforms (1) |
GPL9052 |
Illumina Genome Analyzer (Homo sapiens) |
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Samples (1) |
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This SubSeries is part of SuperSeries: |
GSE69153 |
RC3H1 posttranscriptionally regulates A20 mRNA and modulates the activity of the IKK/NF-kB pathway |
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Relations |
BioProject |
PRJNA203446 |
SRA |
SRP022892 |