Guo Liang, Louis Irina Vlasova-St, Bohjanen Paul R
Department of Medicine, Division of Infectious Diseases and International Medicine, Program in Infection and Immunity, University of Minnesota, Minneapolis, MN 55455, USA.
Institute for Molecular Virology Training Program, University of Minnesota, Minneapolis, MN 55455, USA.
Curr Trends Immunol. 2018;19:33-40.
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.
细胞因子和细胞因子信号通路对于调节细胞功能至关重要，这些功能包括细胞生长、增殖、分化和细胞死亡。细胞因子调节诸如免疫反应等生理过程并维持免疫稳态，它们还介导诸如自身免疫性疾病和癌症等病理状况。因此，细胞因子表达的精确控制以及细胞因子信号的转导在转录和转录后水平上受到严格调控。特别是，mRNA稳定性水平的转录后调控对于协调细胞因子表达和细胞因子信号传导至关重要。许多细胞因子转录本含有富含AU的元件（ARE），而编码细胞因子信号通路众多组分的转录本含有富含GU的元件（GRE）。ARE和GRE是介导mRNA快速降解的mRNA衰变元件。通过ARE和GRE介导的衰变机制，免疫细胞在免疫反应过程中选择性且特异性地调节细胞因子网络。在包括癌症在内的疾病状态中，观察到编码细胞因子或细胞因子信号通路组分的含ARE或GRE转录本的异常表达和稳定性。在本综述中，我们聚焦于ARE和GRE在mRNA稳定性水平上调节细胞因子表达和信号转导中的作用。
