1. and Other Unstable mRNAs
The Wnt/-Catenin→Pitx2 Pathway Controls
the Turnover of Pitx2
and Other Unstable mRNAs
Molecular Cell, Vol. 12, 1201–1211, November, 2003.

2. Identification of a Wnt/Dvl/b-Catenin --> Pitx2 pathway mediating cell-type-specific proliferation during development Kioussi et al. Cell. 2002, 111(5):673-85

3. Baek et al. Proc Natl Acad Sci U S A. 2003, 100(6):3245-50
Regulated subset of G1 growth-control genes in response to derepression by the Wnt pathway.
Baek et al. Proc Natl Acad Sci U S A. 2003, 100(6):
From previous report
Rapid induction of Pitx2 by Wnt
During development, tightly regulated expression of Pitx2 in time and space
It might exist additional mechanism that regulates Pitx2 expression
as well as TCF/LEF dependent manner
Regulation of gene expression
Transcriptional regulation
Regulation of RNA stability

4. Rapid mRNA degradation requires three components
Figure.1
Instability elements: ARE
Trans-acting factors: ARE-BPs
Enzyme: exosome

5. Altogether these data suggest that
The expression of Pitx2 can be regulated at the level of its transcript turnover.
Two regions, the CDS and the 3′UTR, contain destabilizing sequences.
Pitx2 3′UTR displays class III ARE mediating exosome-dependent mRNA degradation

6. Figure.2
Altogether our findings suggest that
the molecular target of Wnt signaling is
the ARE-mediated decay of the mRNA.
Wnt signaling regulates both transcriptional and mRNA turnover changes.

7. Figure.3
Specific interaction of ARE-BPs with Pitx2 3`-UTR in vitro.
Changes in ARE-BPs interacted with
Pitx2 RNA by Wnt signaling
Wnt signaling induces changes in
the nucleocytoplasmic distribution of ARE-BPs

8. Figure.5
Pitx2 plays a central role in the Wnt-activated regulatory pathway that stabilizes Pitx2, Cyclin D1, Cyclin D2, and c-Jun RNAs.

9. ARE-BPs subcellular localization
Wnt
b-catenin
LEF/TCF
ARE-BPs subcellular localization
TTP-ARE
KSRP-ARE
HuR-ARE
mRNA stabilization
C-Jun
Cyclin D1
Pitx2
CyclinD2