标题：Nuclear to cytoplasmic translocation of heterogeneous nuclear ribonucleoprotein U enhances TLR-induced proinflammatory cytokine production by stabilizing mRNAs in macrophages
作者机构：[Zhao, W] Department of Immunology, Shandong University School of Medicine, Jinan, Shandong 250012, China;[ Wang, L] Department of Immunology, Shandon 更多
通讯作者地址：[Gao, CJ]Shandong Univ, Sch Med, Dept Immunol, Jinan 250012, Shandong, Peoples R China.
来源：The Journal of Immunology: Official Journal of the American Association of Immunologists
摘要：TLR signaling is associated with the transcription of various proinflammatory cytokines, including TNF-α, IL-6, and IL-1β. After transcription, the mRNA of these proinflammatory cytokines needs to be tightly controlled at the posttranscriptional level to achieve an optimal expression. However, the precise mechanism of posttranscriptional regulation is not fully understood. In the current study, we found the expression of heterogeneous nuclear ribonucleoprotein U (hnRNP U), also termed scaffold attachment factor A, was greatly induced by TLR stimulation in macrophages. Knockdown of hnRNP U expression greatly attenuated TLR-induced expression of TNF-α, IL-6, and IL-1β, but not IL-12, whereas hnRNP U overexpression greatly increased TLR-induced expression of TNF-α, IL-6, and IL-1β. Furthermore, hnRNP U knockdown accelerated the turnover and decreased the t 1/2 of TNF-α, IL-6, and IL-1β mRNA. RNA immunoprecipitation demonstrated that hnRNP U bound to the mRNA of these proinflammatory cytokines through the RGG motif. Importantly, we showed that TLR stimulation provided a stimulus for hnRNP U nuclear to cytoplasmic translocation. Therefore, we propose that hnRNP U induced by TLR signaling binds to the mRNA of a subset of proinflammatory cytokines and positively regulates the expression of these cytokines by stabilizing mRNA.