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-κ B pathway regulators such as Iκ Bα 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 Iκ B kinase and NF-κ B activities, demonstrating that RC3H1 can modulate the activity of the IKK/NF-κ B pathway.
| Original language | English |
|---|---|
| Article number | 7367 |
| Journal | Nature communications |
| Volume | 6 |
| DOIs | |
| Publication status | Published - Jul 14 2015 |
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All Science Journal Classification (ASJC) codes
- Chemistry(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Physics and Astronomy(all)
Cite this
RC3H1 post-transcriptionally regulates A20 mRNA and modulates the activity of the IKK/NF-κ B pathway. / Murakawa, Yasuhiro; Hinz, Michael; Mothes, Janina; Schuetz, Anja; Uhl, Michael; Wyler, Emanuel; Yasuda, Tomoharu; Mastrobuoni, Guido; Friedel, Caroline C.; Dölken, Lars; Kempa, Stefan; Schmidt-Supprian, Marc; Blüthgen, Nils; Backofen, Rolf; Heinemann, Udo; Wolf, Jana; Scheidereit, Claus; Landthaler, Markus.
In: Nature communications, Vol. 6, 7367, 14.07.2015.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - RC3H1 post-transcriptionally regulates A20 mRNA and modulates the activity of the IKK/NF-κ B pathway
AU - Murakawa, Yasuhiro
AU - Hinz, Michael
AU - Mothes, Janina
AU - Schuetz, Anja
AU - Uhl, Michael
AU - Wyler, Emanuel
AU - Yasuda, Tomoharu
AU - Mastrobuoni, Guido
AU - Friedel, Caroline C.
AU - Dölken, Lars
AU - Kempa, Stefan
AU - Schmidt-Supprian, Marc
AU - Blüthgen, Nils
AU - Backofen, Rolf
AU - Heinemann, Udo
AU - Wolf, Jana
AU - Scheidereit, Claus
AU - Landthaler, Markus
PY - 2015/7/14
Y1 - 2015/7/14
N2 - 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-κ B pathway regulators such as Iκ Bα 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 Iκ B kinase and NF-κ B activities, demonstrating that RC3H1 can modulate the activity of the IKK/NF-κ B pathway.
AB - 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-κ B pathway regulators such as Iκ Bα 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 Iκ B kinase and NF-κ B activities, demonstrating that RC3H1 can modulate the activity of the IKK/NF-κ B pathway.
UR - http://www.scopus.com/inward/record.url?scp=84937047445&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84937047445&partnerID=8YFLogxK
U2 - 10.1038/ncomms8367
DO - 10.1038/ncomms8367
M3 - Article
C2 - 26170170
AN - SCOPUS:84937047445
VL - 6
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 7367
ER -