@Article{Murakawa_Hinz_Mothes-post_regul_mRNA-2015, author = {Murakawa, Yasuhiro and Hinz, Michael and Mothes, Janina and Schuetz, Anja and Uhl, Michael and Wyler, Emanuel and Yasuda, Tomoharu and Mastrobuoni, Guido and Friedel, Caroline C. and Dolken, Lars and Kempa, Stefan and Schmidt-Supprian, Marc and Bluthgen, Nils and Backofen, Rolf and Heinemann, Udo and Wolf, Jana and Scheidereit, Claus and Landthaler, Markus}, title = {{RC3H1} post-transcriptionally regulates {A20} {mRNA} and modulates the activity of the {IKK}/{NF}-{kappaB} pathway}, journal = {Nat Commun}, year = {2015}, volume = {6}, number = {}, pages = {7367}, user = {backofen}, pmid = {26170170}, doi = {10.1038/ncomms8367}, issn = {2041-1723}, abstract = {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 approximately 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-kappaB pathway regulators such as IkappaBalpha 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 IkappaB kinase and NF-kappaB activities, demonstrating that RC3H1 can modulate the activity of the IKK/NF-kappaB pathway.} }