下调Tra2α和Tra2β通过调节MyD88 mRNA选择性剪接抑制巨噬细胞脂多糖诱导的炎症。

IF 3.7 2区 生物学 Q3 CELL BIOLOGY
Yu Fu, Luyao Zhang, Yanjing Wang, Bo Cheng, Weiye Shi, Peiyuan Chen, Jinyu Liu, Xiaolei Zhou, Yingze Wang
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引用次数: 0

摘要

RNA结合蛋白(rbp)在炎症过程的转录后调控中起着关键作用。Transformer-2 (Tra2)是一种进化上保守的RBP,它调节mRNA的选择性剪接,在脊椎动物中编码两种同源蛋白,Tra2α和Tra2β。Tra2α或Tra2β的失调可能导致几种炎症性疾病的发生。然而,Tra2α和Tra2β在炎症中的作用尚不清楚。在本研究中,脂多糖(LPS)刺激RAW264.7巨噬细胞上调Tra2α和Tra2β的表达水平。下调Tra2α或Tra2β可抑制LPS诱导的炎症因子的表达。值得注意的是,联合抑制Tra2α和Tra2β可协同减少lps激活的炎症,并抑制NFκB和MAPK通路的激活。髓样分化主要反应基因88 (MyD88)是TLR4通路的重要接头,表达剪接变体MyD88- l和MyD88- s,分别具有促炎和抗炎作用。我们发现Tra2α和Tra2β蛋白与MyD88 mRNA相互作用。此外,Tra2α和Tra2β下调可促进MyD88-S mRNA变体的表达,从而调节炎症反应。因此,我们的研究结果表明,在lps刺激的巨噬细胞中,Tra2α和Tra2β通过调节MyD88的选择性剪接来协同调节炎症。这些对tra2介导的巨噬细胞炎症调节的机制见解可能为治疗炎症性疾病提供新的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Downregulation of Tra2α and Tra2β suppresses lipopolysaccharide-induced inflammation in macrophages by regulating MyD88 mRNA alternative splicing.

RNA binding proteins (RBPs) play a pivotal role in the posttranscriptional regulation of inflammatory processes. Transformer-2 (Tra2) is an evolutionarily conserved RBP that regulates mRNA alternative splicing, encoding two homologous proteins in vertebrates, Tra2α and Tra2β. Dysregulation of Tra2α or Tra2β may lead to the development of several inflammatory diseases. However, the roles of Tra2α and Tra2β in inflammation remain unclear. In the current research, the expression levels of Tra2α and Tra2β were upregulated in RAW264.7 macrophage cells stimulated by lipopolysaccharide (LPS). Downregulation of Tra2α or Tra2β inhibited the expression of inflammatory factors induced by LPS. Notably, combined suppression of Tra2α and Tra2β cooperatively reduced LPS-activated inflammation and suppressed the activation of NFκB and MAPK pathways. Myeloid differentiation primary response gene 88 (MyD88), a crucial adaptor in the TLR4 pathway, expresses splicing variants MyD88-L and MyD88-S, which exert pro-inflammatory and anti-inflammatory effects, respectively. We found that Tra2α and Tra2β proteins interacted with MyD88 mRNA. Moreover, downregulation of Tra2α and Tra2β promoted the expression of MyD88-S mRNA variants, thereby modulating the inflammatory response. Therefore, our findings demonstrated that Tra2α and Tra2β cooperatively regulated inflammation by modulating the alternative splicing of MyD88 in LPS-stimulated macrophages. These mechanistic insights into Tra2-mediated regulation of macrophage inflammation may provide novel therapeutic targets for treating inflammatory diseases.

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来源期刊
Molecular and Cellular Biochemistry
Molecular and Cellular Biochemistry 生物-细胞生物学
CiteScore
8.30
自引率
2.30%
发文量
293
审稿时长
1.7 months
期刊介绍: Molecular and Cellular Biochemistry: An International Journal for Chemical Biology in Health and Disease publishes original research papers and short communications in all areas of the biochemical sciences, emphasizing novel findings relevant to the biochemical basis of cellular function and disease processes, as well as the mechanics of action of hormones and chemical agents. Coverage includes membrane transport, receptor mechanism, immune response, secretory processes, and cytoskeletal function, as well as biochemical structure-function relationships in the cell. In addition to the reports of original research, the journal publishes state of the art reviews. Specific subjects covered by Molecular and Cellular Biochemistry include cellular metabolism, cellular pathophysiology, enzymology, ion transport, lipid biochemistry, membrane biochemistry, molecular biology, nuclear structure and function, and protein chemistry.
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