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  - 
TY  - JOUR
A1  - Drgonova, Jana
A1  - Walther, Donna
A1  - Hartstein, G Luke
A1  - Bukhari, Mohammad O
A1  - Baumann, Michael H
A1  - Katz, Jonathan
A1  - Hall, F Scott
A1  - Arnold, Elizabeth R
A1  - Flax, Shaun
A1  - Riley, Anthony
A1  - Rivero, Olga
A1  - Lesch, Klaus-Peter
A1  - Troncoso, Juan
A1  - Ranscht, Barbara
A1  - Uhl, George R
T1  - Cadherin 13: Human cis-Regulation and Selectively Altered Addiction Phenotypes and Cerebral Cortical Dopamine in Knockout Mice
JF  - Molecular Medicine
N2  - The Cadherin 13 (CDH13) gene encodes a cell adhesion molecule likely to influence development and connections of brain circuits that modulate addiction, locomotion and cognition, including those that involve midbrain dopamine neurons. Human CDH13 mRNA expression differs by more than 80% in postmortem cerebral cortical samples from individuals with different CDH13 genotypes, supporting examination of mice with altered CDH13 expression as models for common human variation at this locus. Constitutive CDH13 knockout mice display evidence for changed cocaine reward: shifted dose response relationship in tests of cocaine-conditioned place preference using doses that do not alter cocaine-conditioned taste aversion. Reduced adult CDH13 expression in conditional knockouts also alters cocaine reward in ways that correlate with individual differences in cortical CDH13 mRNA levels. In control and comparison behavioral assessments, knockout mice display modestly quicker acquisition of rotarod and water maze tasks, with a trend toward faster acquisition of 5-choice serial reaction time tasks that otherwise displayed no genotype-related differences. They display significant differences in locomotion in some settings, with larger effects in males. In assessments of brain changes that might contribute to these behavioral differences, there are selective alterations of dopamine levels, dopamine/metabolite ratios, dopaminergic fiber densities and mRNA encoding the activity dependent transcription factor npas4 in cerebral cortex of knockout mice. These novel data and previously reported human associations of CDH13 variants with addiction, individual differences in responses to stimulant administration and attention deficit hyperactivity disorder (ADHD) phenotypes suggest that levels of CDH13 expression, through mechanisms likely to include effects on mesocortical dopamine, influence stimulant reward and may contribute modestly to cognitive and locomotor phenotypes relevant to ADHD.
KW  - Cadherin (CDH13)
KW  - CDH13 mRNA
KW  - Attention Deficit Hyperactivity Disorder (ADHD)
KW  - CDH13 Expression
KW  - Human CDH13
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165842
VL  - 22
ER  -