Post-transcriptional regulation of cytokine expression and signaling

Cytokines and cytokine signaling pathways are crucial for regulating cellular functions, including cell growth, proliferation, differentiation, and cell death. Cytokines regulate physiological processes such as immune responses and maintain immune homeostasis, and they also mediate pathological conditions such as autoimmune diseases and cancer. Hence, the precise control of the expression of cytokines and the transduction of cytokine signals is tightly regulated at transcriptional and post-transcriptional levels. In particular, post-transcriptional regulation at the level of mRNA stability is critical for coordinating cytokine expression and cytokine signaling. Numerous cytokine transcripts contain AU-rich elements (AREs), whereas transcripts encoding numerous components of cytokine signaling pathways contain GU-rich elements (GREs). AREs and GREs are mRNA decay elements that mediate rapid mRNA degradation. Through ARE- and GRE-mediated decay mechanisms, immune cells selectively and specifically regulate cytokine networks during immune responses. Aberrant expression and stability of ARE- or GRE-containing transcripts that encode cytokines or components of cytokine signaling pathways are observed in disease states, including cancer. In this review, we focus on the role of AREs and GREs in regulating cytokine expression and signal transduction at the level of mRNA stability.