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.
|Original language||English (US)|
|Number of pages||8|
|Journal||Current Trends in Immunology|
|State||Published - 2018|
Bibliographical noteFunding Information:
This work was supported by NIH grants AI057484 and AI072068 to P. R. B. L. G. was funded through NIH grant T32 AI83196. I.V-S. was funded through a fellowship from the Lymphoma Research Foundation and supported by start-up funds from the Department of Medicine at the University of Minnesota.
- Cytokine signaling
- Immune responses
- MRNA decay
- Post-transcriptional regulation
- mRNA stability