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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-12

AUTHORS

Yasuhiro Murakawa, Michael Hinz, Janina Mothes, Anja Schuetz, Michael Uhl, Emanuel Wyler, Tomoharu Yasuda, Guido Mastrobuoni, Caroline C. Friedel, Lars Dölken, Stefan Kempa, Marc Schmidt-Supprian, Nils Blüthgen, Rolf Backofen, Udo Heinemann, Jana Wolf, Claus Scheidereit, Markus Landthaler

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. More... »

PAGES

7367

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ncomms8367

    DOI

    http://dx.doi.org/10.1038/ncomms8367

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1001698215

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/26170170


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