SRSF10 regulates alternative splicing and is required for adipocyte differentiation

Area of Science:

• Molecular Biology
• Cell Biology
• Metabolic Research

Background:

• Adipocyte differentiation involves significant alternative splicing events.
• The roles of specific splicing factors, like SRSF10, in adipogenesis are not well understood.
• Defects in adipose tissue development are linked to metabolic disorders.

Purpose of the Study:

• To investigate the role of splicing factor SRSF10 in adipocyte differentiation and white adipose tissue (WAT) development.
• To identify SRSF10-regulated alternative splicing events critical for adipogenesis.
• To elucidate the mechanism by which SRSF10 influences lipin1 splicing and function.

Main Methods:

• Transcriptome sequencing (RNA-seq) of embryonic fibroblast cells.
• Analysis of splicing factor SRSF10-deficient mice models.
• Molecular biology techniques to study gene splicing and protein function.
• In vitro experiments to validate splicing events and rescue adipogenic defects.

Main Results:

• Mice lacking SRSF10 showed impaired subcutaneous WAT development due to defective adipogenic differentiation.
• SRSF10 regulates the alternative splicing of lipin1, promoting the production of the lipin1α isoform.
• Lipin1α, generated by SRSF10-mediated exon 7 skipping, is essential for initial adipocyte differentiation.
• Restoration of lipin1α expression rescued SRSF10-deficiency-induced adipogenic defects.

Conclusions:

• SRSF10 is an essential regulator of adipocyte differentiation and WAT development.
• SRSF10 controls adipogenesis by modulating lipin1 pre-mRNA splicing to produce the critical lipin1α isoform.
• This study provides novel insights into the function of SRSF10 in regulating gene splicing for metabolic processes.