The beta-catenin/TCF4 pathway modifies alternative splicing through modulation of SRp20 expression

Area of Science:

• Molecular Biology
• Cell Signaling
• Cancer Biology

Background:

• The Wnt signaling pathway is crucial for cellular processes and is often dysregulated in colorectal cancer.
• Beta-catenin stabilization and nuclear translocation are key events in Wnt pathway activation.
• Beta-catenin/TCF transcription factors regulate the expression of target genes.

Purpose of the Study:

• To identify novel target genes of the beta-catenin/TCF4 signaling pathway.
• To investigate the role of beta-catenin/TCF4 signaling in regulating gene transcription and alternative splicing.
• To explore the functional consequences of SRp20 modulation by this pathway.

Main Methods:

• Utilized gene reporter assays (luciferase) to assess promoter activity.
• Employed gene transfection and dominant-negative constructs to manipulate beta-catenin/TCF4 signaling.
• Analyzed changes in gene expression (transcript and protein levels) and alternative splicing patterns.

Main Results:

• SRp20 was identified as a novel target gene of beta-catenin/TCF4 signaling.
• Activation of beta-catenin/TCF4 signaling increased SRp20 transcription and protein levels.
• Increased SRp20 levels modulated alternative splicing of reporter genes and endogenous CD44.

Conclusions:

• The beta-catenin/TCF4 pathway controls both gene transcription and alternative splicing.
• SRp20 acts as a mediator linking Wnt signaling to alternative splicing.
• This highlights a coordinated regulation of gene expression at multiple layers by signaling pathways.