Dissemin is shutting down on January 1st, 2025

Published in

Nature Research, Nature Communications, 1(6), 2015

DOI: 10.1038/ncomms8367

Links

Tools

Export citation

Search in Google Scholar

RC3H1 post-transcriptionally regulates A20 mRNA and modulates the activity of the IKK/NF-κB pathway

Journal article published in 2015 by Yasuhiro Murakawa, Michael Hinz, Janina Mothes, Anja Schuetz, Michael Uhl, Emanuel Wyler, Friedel Cc, Tomoharu Yasuda, Guido Mastrobuoni, Caroline C. Friedel ORCID, Lars Dölken, Stefan Kempa, Marc Schmidt-Supprian, Nils Blüthgen, Rolf Backofen ORCID and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

Full text: Download

Green circle
Preprint: archiving allowed
Upload
Red circle
Postprint: archiving forbidden
Green circle
Published version: archiving allowed
Upload
Policy details
Data provided by SHERPA/RoMEO

Abstract

AbstractThe 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.