The cytokine interlukin-6 (IL-6) is a vital mediator of the innate immune response, and a pleiotropic regulator of cellular function. Its involvement in autoimmune and inflammatory diseases, and cancer is illustrated by the clinical benefits of IL-6 blockade. Thus, there is a necessity to control the IL-6 production at transcriptional and post-transcriptional level. Post-transcriptional regulation that controls mRNA stability and translation appears to play a critical role in the regulation of not only Il6 expression but also Stat3, Ox40, T-bet and IL-17-induced expression of mRNAs by RNA-binding proteins. Few years ago, our group has reported a novel role of AT-rich interactive domain-containing protein 5A (Arid5a) in the post-transcriptional regulation of Il6 mRNA via binding to its 3’UTR thereby augmenting autoimmune disease, EAE. However, Regnase-1, an RNase, degrades mRNAs of multiple inflammatory genes such as Il6, Stat3, Ox40 etc. and contributes in the regulation of their mRNA stability by binding to 3’UTR of mRNAs. We found that Arid5a binds to the same region on 3’UTRs where Regnase-1 binds, and interferes Regnase-1 function thus, exacerbates autoimmune and inflammatory diseases. Briefly, our laboratory has identified several inflammatory mRNAs as targets of Arid5a and its contribution in many autoimmune and inflammatory disease such as experimental autoimmune encephalitis, sepsis, rheumatoid arthritis, acute lung injury etc. Furthermore, recent studies have shown Arid5a contribution in tumorigenesis too such as in lung cancer. Here, we highlight some recent progresses in Arid5a research to better understand Arid5a-mediated molecular mechanisms, and their relevance to Arid5a as promising therapeutic agent in immunological disorders.
Posttranscriptional regulation, Arid5a, IL-6, Inflammation, Immunity