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iNature heterogeneous nuclear ribonucleoproteins (hnRNPs) are a family of RNA-binding proteins that play important roles in various biological processes
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However, the roles of members of hnRNPs in immunity and inflammation remain to be fully understood
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On April 13, 2022, the Chinese Academy of Medical Sciences/Peking Union Medical College Cao Xuetao team published a research paper titled "RNA-binding protein hnRNP UL1 binds κB sites to attenuate NF-κB-mediated inflammation" in the Journal of Autoimmunity.
The study The hnRNP UL1 was identified as a negative regulator of NF-κB-mediated inflammation by functional screening of hnRNPs members in LPS-stimulated macrophage inflammatory responses
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hnRNP UL1 restricts NF-κB-triggered transcriptional expression of proinflammatory cytokines to innate stimuli
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 Perturbation of hnRNP UL1 enhances proinflammatory cytokine production in macrophages
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Deficiency of hnRNP UL1 in vivo increases proinflammatory cytokine production upon exposure to LPS
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Therefore, the expression of hnRNP UL1 is decreased in peripheral blood mononuclear cells of rheumatoid arthritis patients
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Mechanistically, hnRNP UL1 competes with NF-κB for binding to the κB site to limit the magnitude and duration of the inflammatory response
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Meanwhile, extensive dynamic binding of hnRNP UL1 to target gene promoters was revealed during the inflammatory response
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In conclusion, this study adds new insights into the role of hnRNPs in NF-κB-mediated inflammation, suggesting a potential therapeutic strategy to control inflammatory autoimmune diseases
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On March 28, 2022, Hou Jin and Cao Xuetao of Naval Medical University jointly published a research paper entitled "Malignant progression of liver cancer progenitors requires KAT7-acetylated and cytoplasm-translocated G-protein GαS" in Hepatology (IF=17) , which used quantitative mass spectrometry-based methods to screen non-aggregated hepatocytes and HcPC-containing aggregates from a DEN-induced HCC mouse model for proteomic analysis to elucidate dysregulated proteins in HcPC
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This study found that the malignant progression of HcPCs requires increased K28 acetylation and cytoplasmic translocation of GαS, resulting in an enhanced response to IL-6 and driving precancerous HcPCs to fully establish HCC, which provides mechanistic insights and potential targets for the prevention of hepatocarcinogenesis ( click to read)
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An appropriate inflammatory response is necessary to eliminate inflammatory stimuli and repair damaged tissue
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However, unresolved or long-standing adverse inflammation can lead to chronic inflammation, cancer, or autoimmune disease
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Since cytokines produced by activated immune cells play a key role in regulating inflammation, blockade agents targeting some pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β, have been shown to be inflammatory autologous Effective therapy for immune diseases
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In particular, IL-6 has received much attention due to its pleiotropic functions and widespread involvement in inflammatory diseases including rheumatoid arthritis (RA) and Castleman's disease
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In addition to chronic inflammatory diseases and cancer, IL-6 serum levels have been an important indicator for assessing the severity of infectious diseases, including COVID-19
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Tocilizumab, a humanized monoclonal antibody targeting the IL-6 receptor, has been shown to improve clinical outcomes in severe and critically ill COVID-19 patients, in addition to its use in the treatment of autoimmune diseases
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Nevertheless, in order to better alleviate the inflammatory pathological damage caused by such autoimmune diseases or infectious diseases, the underlying mechanism of its anti-inflammatory effect remains to be further studied
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Transcriptional or post-transcriptional regulation of inflammatory cytokines has long been regarded as a direct factor determining the outcome of inflammation
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The transcription factor NF-κB has been reported to effectively trigger a large number of pro-inflammatory cytokines
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However, the negative regulator value of pro-inflammatory cytokines that may exhibit anti-inflammatory functions remains to be further investigated
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Schematic diagram of the article (picture from Journal of Autoimmunity) Heterogeneous nuclear ribonucleoproteins (hnRNPs) are a large class of RNA-binding proteins that are important in many aspects of nucleic acid metabolism
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In addition to their abundance in the nucleus, features including RNA-binding domains, helper domains, and shuttling between the nucleus and cytoplasm define the general characteristics of hnRNPs
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hnRNP A2/B1 recognizes pathogenic DNA and initiates IFN-α/β production
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SAFA (aka hnRNP U) has been reported to monitor viral RNA and promote immunity by activating antiviral enhancers and super-enhancers
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Although the functions of hnRNPs beyond RNA metabolism have been widely reported, the role of hnRNPs in the regulation of inflammation remains to be elucidated
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To systematically study the role of hnRNPs in the regulation of inflammation, functional screening of 26 hnRNPs, including typical hnRNPs and hnRNPs-like proteins, was performed
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This study used Il6 mRNA expression as a readout to decipher the role of hnRNP in LPS-stimulated inflammatory responses in mouse primary peritoneal macrophages
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 With this approach, the study identified hnRNP UL1 as an important suppressor of proinflammatory cytokine production
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In vivo experimental validation and in vitro analysis of clinical samples support a critical role of hnRNP UL1 in suppressing inflammation
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This study found that hnRNP UL1 binds to the κB site to antagonize NF-κB binding, thereby inhibiting the transcription of inflammatory cytokines during the inflammatory response
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In conclusion, this study adds new insights into the role of hnRNPs in NF-κB-mediated inflammation, suggesting a potential therapeutic strategy to control inflammatory autoimmune diseases
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Reference message: https://doi.
org/10.
1016/j.
jaut.
2022.
102828