Identification of Heat shock protein family A member 5 (HSPA5) targets involved in nonalcoholic fatty liver disease

Abstract Background HSPA5 is an endoplasmic reticulum chaperone which regulates cell metabolism, especially lipid metabolism. There are many reports about the role of HSPA5 in regulating cell function but the role on HSPA5 binding to RNA and its biological function in nonalcoholic fatty liver disease is still lacking. Method In the present study, the ability of HSPA5 to modulate the alternative splicing ( AS ) of cellular genes was assessed using RT-PCR on 89 nonalcoholic fatty liver disease-associated genes. RNA immunoprecipitation coupled to RNA sequencing (RIP-Seq) assays were also performed to identify cellular mRNAs bound by HSPA5. Results Upon HSPA5 expression, we detected modifications to the AS profiles of 89 genes involved in nonalcoholic fatty liver disease. Moreover, we show that HSPA5 modulates the expression levels of various splicing factors such as EGFR, NEAT1, LRP1 and TGFß1 which are important for the pathology of nonalcoholic fatty liver disease. Finally, RNA immunoprecipitation coupled to RIP-Seq assays demonstrated that HSPA5 immuno-precipitates specific cellular mRNAs. Conclusion This is the first report demonstrating that HSPA5 protein modulates the AS profiles of genes important in nonalcoholic fatty liver disease and binds lncRNA and mRNA linked to nonalcoholic fatty liver disease.