Tissue-specific SEC31A alternative splicing is regulated by RBM47 and controls lipid transport

Area of Science:

• Cell Biology
• Molecular Biology
• Genetics

Background:

• Coat protein complex II (COPII) is crucial for protein secretion.
• Mechanisms for secreting large cargo, such as procollagens and chylomicrons, via COPII vesicles remain unclear due to vesicle size limitations.

Purpose of the Study:

• To investigate alternative splicing as a regulatory mechanism for large cargo secretion.
• To identify tissue-specific alternative splicing events in secretion-associated genes.
• To uncover the regulators of tissue-specific alternative splicing in secretion pathways.

Main Methods:

• RNA-sequencing (RNA-seq) analysis of human tissues to identify alternative splicing.
• Functional analysis of a novel SEC31A exon.
• Correlation analysis between SEC31A splicing and RNA-binding protein expression.
• In silico prediction and experimental validation of splicing regulators.

Main Results:

• Identified tissue-specific alternative splicing in secretion-associated genes, including a novel exon in SEC31A.
• Demonstrated that SEC31A exon inclusion enhances lipid transport, linking alternative splicing to large cargo secretion.
• Identified and validated RBM47 as a trans-acting factor regulating SEC31A alternative splicing.

Conclusions:

• Alternative splicing of SEC31A provides a regulatory mechanism for the secretion of large cargo.
• RBM47 is a key regulator of SEC31A alternative splicing, impacting lipid transport.
• An in silico approach can effectively identify trans-acting factors controlling tissue-specific alternative splicing.