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| Item Type: | Article |
|---|---|
| Title: | RC3H1 post-transcriptionally regulates A20 mRNA and modulates the activity of the IKK/NF-κB pathway |
| Creators Name: | Murakawa, Y., Hinz, M., Mothes, J., Schuetz, A., Uhl, M., Wyler, E., Yasuda, T., Mastrobuoni, G., Friedel, C.C., Dölken, L., Kempa, S., Schmidt-Supprian, M., Blüthgen, N., Backofen, R., Heinemann, U., Wolf, J., Scheidereit, C. and Landthaler, M. |
| Abstract: | The RNA-binding protein RC3H1 (also known as ROQUIN) promotes TNFα mRNA decay via a 3'UTR constitutive decay element (CDE). Here we applied PAR-CLIP to human RC3H1 to identify ~3,800 mRNA targets with >16,000 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 post-transcriptional regulation of the DNA damage response. Intriguingly, RC3H1 affects expression of the NF-κB pathway regulators such as IκBα and A20. RC3H1 uses ROQ 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 IκB kinase and NF-κB activities, demonstrating that RC3H1 can modulate the activity of the IKK/NF-κB pathway. |
| Keywords: | Binding Sites, DNA Damage, DNA-Binding Proteins, Gene Expression Regulation, Gene Knockdown Techniques, HEK293 Cells, I-κB Proteins, Intracellular Signaling Peptides and Proteins, Messenger RNA, NF-κB, Nuclear Proteins, Polyacrylamide Gel Electrophoresis, Post-Transcriptional RNA Processing, RNA Stability, RNA-Binding Proteins, Signal Transduction, Ubiquitin-Protein Ligases, Western Blotting |
| Source: | Nature Communications |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Volume: | 6 |
| Page Range: | 7367 |
| Date: | 14 July 2015 |
| Official Publication: | https://doi.org/10.1038/ncomms8367 |
| PubMed: | View item in PubMed |
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