lncRNA NORAD通过与STAT3的相互作用来调节人类细胞中的STAT3/STAT1平衡和先天免疫反应
Amir Argoetti1, Dor Shalev1, Galia Polyak1
1Technion-Israel Institute of Technology, Faculty of Biology, Emerson building, Haifa, Israel.
Nature communications
|January 10, 2025
概括
长非编码RNA NORAD通过控制STAT3定位来调节免疫反应,影响人类细胞中的抗病毒基因激活. 这种相互作用对宿主防御至关重要,并且在人类中独特地进化.
科学领域:
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
- 遗传学 遗传学 是一个
背景情况:
- 长非编码RNAs (lncRNAs) 是细胞功能的关键调节者.
- lncRNA NORAD以其在维持DNA稳定中的作用而闻名.
- 信号转换器和转录3激活器 (STAT3) 是一种与免疫相关的转录因子.
研究的目的:
- 研究人类细胞中 lncRNA NORAD 和转录因子 STAT3 之间的相互作用.
- 了解NORAD在免疫调节和抗病毒反应中的作用.
- 探索人类宿主防御中这种相互作用的进化方面.
主要方法:
- 在人类胚胎和分化的细胞中进行了NORAD的敲除实验.
- 使用细胞检测分析了STAT3局部化 (细胞质与核) .
- 检查了来自体外实验和临床样本的RNA表达数据.
- 进行了NORAD的进化保护分析.
主要成果:
- 诺拉德促进STAT3核定位,并抑制抗病毒基因激活.
- 在NORAD缺乏的细胞中,STAT3仍然在细胞质中,增强STAT1介导的抗病毒活性.
- 在实验和临床环境中,NORAD水平在病毒感染后降低.
- 诺拉德的确定的调节功能似乎是人类特异性的,与Alu元素插入有关.
结论:
- 诺拉德作为STAT3介导免疫抑制的关键调节器.
- 这项研究阐明了lncRNA参与免疫调节的新机制.
- 这些发现突出了NORAD在人类宿主防御的进化适应中的作用.
相关概念视频
lncRNA - Long Non-coding RNAs
8.5K
In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
8.5K
The JAK-STAT Signaling Pathway
8.7K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
8.7K
NF-κB-dependent Signaling Pathway
7.2K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
7.2K
Regulation of Expression at Multiple Steps
868
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
868
mTOR Signaling and Cancer Progression
3.7K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.7K
Types of RNA
5.6K
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in regulating gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA Performs Diverse...
RNA Performs Diverse...
5.6K


