Nuclear to cytoplasmic translocation of heterogeneous nuclear ribonucleoprotein U enhances TLR-induced proinflammatory cytokine production by stabilizing mRNAs in macrophages

The Journal of Immunology : Official Journal of the American Association of Immunologists
Wei ZhaoChengjiang Gao

Abstract

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 proinflamma...Continue Reading

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Citations

Jan 4, 2013·PloS One·Shuzhen GuoEng H Lo
Mar 2, 2016·Proceedings of the National Academy of Sciences of the United States of America·Samiran MondalTasuku Honjo
Sep 2, 2016·Proceedings of the National Academy of Sciences of the United States of America·Hironori NishitsujiKunitada Shimotohno
Oct 7, 2016·Frontiers in Cellular and Infection Microbiology·Xiaopeng ZhangXiancai Rao
Oct 11, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yajing LuRui Zhou
Feb 27, 2014·Biotechnology & Genetic Engineering Reviews·Takashi Mino, Osamu Takeuchi
Feb 14, 2014·The Journal of Biological Chemistry·Xueling LiAndrzej Kudlicki
Sep 28, 2017·International Journal of Molecular Medicine·Hongjun BianJianni Qi

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