BAF57/ SMARCE1 Interacting with Splicing Factor SRSF1 Regulates Mechanical Stress-Induced Alternative Splicing of Cyclin D1

• Main Authors: Jianguo Feng, Xichao Xu, Xin Fan, Qian Yi, Liling Tang
• Format: Article
• Language: English
• Published: MDPI AG 2021-02-01
• Series: Genes
• Subjects: alternative splicing; BAF57/ SMARCE1; <i>cyclin D1</i>; mechanical strain
• Online Access: https://www.mdpi.com/2073-4425/12/2/306

Cyclin D1 regulates cyclin-dependent protein kinase activity of the cell cycle, and<i> cyclin D1</i> alternative splicing generates a <i>cyclin D1b</i> isoform, acting as a mediator of aberrant cellular proliferation. As alternative splicing processes are sensitive to mechanical stimuli, whether the alternative splicing of <i>cyclin D1</i> is regulated by mechanical stress and what kinds of factors may act as the regulator of mechano-induced alternative splicing remain unknown. <b>Methods:</b> The alternative splicing of <i>Cyclin D1</i> was examined using reverse transcription polymerase chain reaction (RT-PCR) in osteoblast cell lines and keratinocyte cells loaded by a cyclic stretch. The expression of splicing factors and switching defective/sucrose non-fermenting (SWI/SNF) complex subunits were detected in stretched cells using real-time quantitative PCR (RT-qPCR). The protein interaction was tested by co-immunoprecipitation assay (Co-IP).<b> Results: </b><i>Cyclin D1</i> expression decreased with its splice variant upregulated in stretched cells. Serine/arginine-rich splicing factor 1 (SRSF1) and SWI/SNF complex subunit Brahma-related gene-1-associated factor 57 (BAF57), also named SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1 (SMARCE1), could respond to mechanical stimuli. Overexpression and knockdown experiments indicated the BAF57/SMARCE1 is probably a critical factor regulating the alternative splicing of cyclin D1. Co-IP showed an interaction between BAF57/SMARCE1 and SRSF1, implying a possible underlying mechanism of the regulator role of BAF57/SMARCE1 in the splicing process of cyclin D1. <b>Conclusions: </b>The splicing factor SRSF1 and BAF57/SMARCE1 are possibly responsible for the mechanical stress-induced alternative splicing of cyclin D1.