An ESRP-regulated splicing programme is abrogated during the epithelial-mesenchymal transition

Area of Science:

• Molecular Biology
• Genetics
• Cell Biology

Background:

• Alternative splicing is a key post-transcriptional mechanism regulating gene expression.
• Epithelial splicing regulatory proteins 1 and 2 (ESRP1 and ESRP2) are critical regulators of splicing during the epithelial-mesenchymal transition (EMT).

Purpose of the Study:

• To comprehensively define the alternative splicing network regulated by ESRPs during EMT.
• To identify novel molecular markers for EMT characterization.
• To elucidate the RNA-binding motif and regulatory map of ESRPs.

Main Methods:

• Bioinformatics analysis to identify ESRP-regulated splicing events.
• Experimental validation of splicing changes and their functional impact.
• Identification of ESRP-binding motifs and RNA maps.

Main Results:

• An extensive ESRP-regulated splicing network comprising hundreds of alternative splicing events was identified.
• Loss of the ESRP-regulated epithelial splicing program induced EMT-associated changes in cell morphology.
• Novel molecular markers for EMT characterization were derived from the splicing signature.
• A high-affinity ESRP-binding motif and predictive RNA map were discovered.

Conclusions:

• ESRPs act as master coordinators of a complex alternative splicing network during EMT.
• This splicing network represents a crucial post-transcriptional layer in EMT gene expression changes.
• The findings provide insights into EMT regulation in development and disease.