TY  - JOUR
A1  - Murakawa, Yasuhiro
A1  - Hinz, Michael
A1  - Mothes, Janina
A1  - Schuetz, Anja
A1  - Uhl, Michael
A1  - Wyler, Emanuel
A1  - Yasuda, Tomoharu
A1  - Mastrobuoni, Guido
A1  - Friedel, Caroline C.
A1  - Dölken, Lars
A1  - Kempa, Stefan
A1  - Schmidt-Supprian, Marc
A1  - Blüthgen, Nils
A1  - Backofen, Rolf
A1  - Heinemann, Udo
A1  - Wolf, Jana
A1  - Scheidereit, Claus
A1  - Landthaler, Markus
T1  - RC3H1 post-transcriptionally regulates A20 mRNA and modulates the activity of the IKK/NF-\(\kappa\)B pathway
JF  - Nature Communications
N2  - The RNA-binding protein RC3H1 (also known as ROQUIN) promotes TNF\(\alpha\) 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-\(\kappa\)B pathway regulators such as I\(\kappa\)B\(\alpha\) 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 I\(\kappa\)B kinase and NF-\(\kappa\)B activities, demonstrating that RC3H1 can modulate the activity of the IKK/NF-\(\kappa\)B pathway.
KW  - large gene lists
KW  - decay
KW  - identification
KW  - stress
KW  - binding protein
KW  - RQQ domain
KW  - autoimmunity
KW  - complex
KW  - degradation
KW  - motifs
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-151596
VL  - 6
IS  - 7367
ER  -