Systematic Analysis of Long Non-Coding RNAs in Inflammasome Activation in Monocytes/Macrophages.

IF 3.6 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-Coding RNA Pub Date : 2023-08-25 DOI:10.3390/ncrna9050050

Na Qian, Rebecca Distefano, Mirolyuba Ilieva, Jens Hedelund Madsen, Sarah Rennie, Shizuka Uchida

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引用次数: 0

Abstract

The NLRP3 inflammasome plays a pivotal role in regulating inflammation and immune responses. Its activation can lead to an inflammatory response and pyroptotic cell death. This is beneficial in the case of infections, but excessive activation can lead to chronic inflammation and tissue damage. Moreover, while most of the mammalian genome is transcribed as RNAs, only a small fraction codes for proteins. Among non-protein-coding RNAs, long non-coding RNAs (lncRNAs) have been shown to play key roles in regulating gene expression and cellular processes. They interact with DNA, RNAs, and proteins, and their dysregulation can provide insights into disease mechanisms, including NLRP3 inflammasome activation. Here, we systematically analyzed previously published RNA sequencing (RNA-seq) data of NLRP3 inflammasome activation in monocytes/macrophages to uncover inflammasome-regulated lncRNA genes. To uncover the functional importance of inflammasome-regulated lncRNA genes, one inflammasome-regulated lncRNA, ENSG00000273124, was knocked down in an in vitro model of macrophage polarization. The results indicate that silencing of ENSG00000273124 resulted in the up-regulation tumor necrosis factor (TNF), suggesting that this lncRNA might be involved in pro-inflammatory response in macrophages. To make our analyzed data more accessible, we developed the web database InflammasomeDB.

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单核细胞/巨噬细胞炎症小体激活中长非编码RNA的系统分析。

NLRP3炎症小体在调节炎症和免疫反应中起着关键作用。它的激活可导致炎症反应和焦性细胞死亡。这在感染的情况下是有益的，但过度激活会导致慢性炎症和组织损伤。此外，尽管哺乳动物基因组的大部分被转录为RNA，但只有一小部分编码蛋白质。在非蛋白质编码RNA中，长非编码RNA（lncRNA）已被证明在调节基因表达和细胞过程中发挥关键作用。它们与DNA、RNA和蛋白质相互作用，它们的失调可以深入了解疾病机制，包括NLRP3炎症小体的激活。在这里，我们系统地分析了先前发表的单核细胞/巨噬细胞中NLRP3炎症小体激活的RNA测序（RNA-seq）数据，以揭示炎症小体调节的lncRNA基因。为了揭示炎症小体调节的lncRNA基因的功能重要性，在巨噬细胞极化的体外模型中敲除了一种炎症小体调节lncRNA，ENSG00000273124。结果表明，ENSG00000273124的沉默导致肿瘤坏死因子（TNF）上调，表明该lncRNA可能参与巨噬细胞的促炎反应。为了使我们分析的数据更容易访问，我们开发了网络数据库InflammatomeDB。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Non-Coding RNA Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

6.70

自引率

4.70%

发文量

审稿时长

10 weeks

期刊介绍： Functional studies dealing with identification, structure-function relationships or biological activity of: small regulatory RNAs (miRNAs, siRNAs and piRNAs) associated with the RNA interference pathway small nuclear RNAs, small nucleolar and tRNAs derived small RNAs other types of small RNAs, such as those associated with splice junctions and transcription start sites long non-coding RNAs, including antisense RNAs, long ''intergenic'' RNAs, intronic RNAs and ''enhancer'' RNAs other classes of RNAs such as vault RNAs, scaRNAs, circular RNAs, 7SL RNAs, telomeric and centromeric RNAs regulatory functions of mRNAs and UTR-derived RNAs catalytic and allosteric (riboswitch) RNAs viral, transposon and repeat-derived RNAs bacterial regulatory RNAs, including CRISPR RNAS Analysis of RNA processing, RNA binding proteins, RNA signaling and RNA interaction pathways: DICER AGO, PIWI and PIWI-like proteins other classes of RNA binding and RNA transport proteins RNA interactions with chromatin-modifying complexes RNA interactions with DNA and other RNAs the role of RNA in the formation and function of specialized subnuclear organelles and other aspects of cell biology intercellular and intergenerational RNA signaling RNA processing structure-function relationships in RNA complexes RNA analyses, informatics, tools and technologies: transcriptomic analyses and technologies development of tools and technologies for RNA biology and therapeutics Translational studies involving long and short non-coding RNAs: identification of biomarkers development of new therapies involving microRNAs and other ncRNAs clinical studies involving microRNAs and other ncRNAs.