Abstract
HSPA5 encodes a chaperone protein, BIP/GRP78, which is also an RNA-binding protein with potential transcriptional and post-transcriptional regulatory functions. To explore the functions of HSPA5 on target genes, we over-expressed HSPA5 (HSPA5-OE) in HeLa cells. Then RNA-seq analysis found 928 genes were significantly differently expressed, among which 460 genes were up-regulated and 468 genes were down-regulated in the HSPA5-OE cells. GO analysis showed that the differently expressed genes were mainly enriched in inflammation and innate Immunity responses. In addition, the up-regulated genes were enriched in the process of cell proliferation and differentiation. Immune-related pathways were also found in the DEGs with KEGG analysis. Furthermore, a total of 659 different alternative splicing events were identified based on the splicing junction reads. And the related genes were enriched in apoptosis, TNF signaling, and NF-kappa B signaling pathways. RT-qPCR experiment proved that the expression of inflammatory/immune-related genes was significantly changed with HSPA5-OE and showed significant difference in alternative splicing of genes involved in the above pathways. Our results suggest that HSPA5 regulates the expression and alternative splicing of inflammatory and immune response genes, which makes a foundation for further exploring the function of HSPA5 as RBP.
Tristetraprolin specifically regulates the expression and alternative splicing of immune response genes in HeLa cells