AT-rich interactive domain-containing protein 5A (ARID5A)

AT-rich interactive domain-containing protein 5A (ARID5A) is a multifaceted protein that functions as both a transcription factor and an RNA-binding protein (RBP), playing a critical role in the regulation of the inflammatory response. It is primarily known for its ability to stabilize the mRNA of pro-inflammatory cytokines, most notably interleukin-6 (IL-6), by binding to their 3' untranslated regions (UTRs) and protecting them from degradation by the endoribonuclease Regnase-1. This stabilization leads to the overproduction of IL-6, which is a key driver in the pathogenesis of various autoimmune and inflammatory diseases, such as rheumatoid arthritis, sepsis, and multiple sclerosis. Beyond its post-transcriptional roles, ARID5A also acts in the nucleus to regulate the transcription of genes involved in Th17 cell differentiation, adipogenesis, and chondrocyte development. In oncology, ARID5A is often upregulated and promotes tumor progression, metastasis, and immune evasion by maintaining a pro-inflammatory microenvironment. While no direct therapeutic inhibitors are currently approved for clinical use, experimental studies have shown that its expression can be modulated by drugs like chlorpromazine and STAT3 inhibitors. Targeting ARID5A represents a promising strategy for treating cytokine-driven pathologies while potentially avoiding the broad immunosuppression associated with direct cytokine blockade.

Other names

MRF1MRF-1RP11-363D14AT-rich interaction domain 5AModulator recognition factor 1

Stabilization of pro-inflammatory mRNA transcripts (e.g., IL-6, STAT3, TBX21) by binding to 3' UTR stem-loop structures and competing with degradative enzymes like Regnase-1 (ZC3H12A).