文章基本信息

标题：Severe Impairment of TNF Post-transcriptional Regulation Leads to Embryonic Death
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作者：Elise Clayer ; Destiny Dalseno ; Andrew Kueh 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2020
卷号：23
期号：11
页码：1-24
DOI：10.1016/j.isci.2020.101726
语种：English
出版社：Elsevier
摘要：SummaryPost-transcriptional regulation mechanisms control mRNA stability or translational efficiency via ribosomes, and recent evidence indicates that it is a major determinant of the accurate levels of cytokine mRNAs. Transcriptional regulation ofTnfhas been well studied and found to be important for the rapid induction ofTnfmRNA and regulation of the acute phase of inflammation, whereas study of its post-transcriptional regulation has been largely limited to the role of the AU-rich element (ARE), and to a lesser extent, to that of the constitutive decay element (CDE). We have identified another regulatory element (NRE) in the 3′ UTR ofTnfand demonstrate that ARE, CDE, and NRE cooperatein vivoto efficiently downregulateTnfexpression and prevent autoimmune inflammatory diseases. We also show that excessive TNF may lead to embryonic death.Graphical AbstractDisplay OmittedHighlights•Three regions ofTnf3′ UTR cooperate to regulate Tnf expression post-transcriptionally•Dysregulation ofTnfpost-transcriptional regulation causes inflammatory diseases•Strong overexpression of TNF leads to vascular failure and embryonic lethalityMolecular Biology; Immunology ; Developmental Biology