长非编码RNA通过表观遗传抑制血管酶转化酶2来增强SARS-CoV-2介导的亡
Weijie Liao1, Tian Zhang2, Jiaxing Cao3
1Department of Hematology and Oncology, Shenzhen University General Hospital, International Cancer Center, Shenzhen University, Shenzhen, Guangdong, China; Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, Guangdong, China.
The Journal of biological chemistry
|October 15, 2025
概括
SARS-CoV-2 感染升级EPB41L4A-AS1 (EAS1),长非编码RNA抑制ACE2表达,加剧COVID-19中器官损伤,并提供潜在的治疗点.
科学领域:
- 分子生物学分子生物学
- 病毒学 病毒学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- ангиотензин转化酶2 (ACE2) 对于器官保护至关重要,但在SARS-CoV-2感染期间受到下调,导致COVID-19多器官功能障碍.
- 精确的机制,特别是那些涉及长非编码RNA (lncRNAs) 的机制,在病毒感染期间驱动ACE2损失,仍然在很大程度上是未知的.
研究的目的:
- 阐明SARS-CoV-2感染导致ACE2下调的机制.
- 确定在冠状病毒感染期间参与调节ACE2表达的特定lncRNAs.
- 在COVID-19病理学背景下调查ACE2失调的功能后果.
主要方法:
- 转录组分析用于在冠状病毒感染时识别差异表达的lncRNAs.
- 染色体免疫沉和记者测试以确定HIF-1α与EAS1位点的结合.
- 生物化学试验以评估GCN5.5对PGC1β的相互作用和乙化.
- 在各种实验条件下分析ACE2基因表达和细胞亡.
主要成果:
- 在包括SARS-CoV-2在内的多种冠状病毒感染中,lncRNA EPB41L4A-AS1 (EAS1) 持续升级.
- SARS-CoV-2 感染激活了 HIF-1α,从而驱动了 EAS1 的表达.
- EAS1招募GCN5,导致PGC1β乙化,破坏PGC1β-PPARγ相互作用并抑制ACE2转录.
- 以EAS1为媒介的ACE2抑制会加剧TNF-α和缺氧诱导的细胞亡,这是严重COVID-19的关键特征.
结论:
- 一个涉及EAS1,GCN5,PGC1β和PPARγ的新型表观遗传途径调解SARS-CoV-2诱导的ACE2抑制,并促进细胞损伤.
- 在不同冠状病毒中EAS1的保存上调表明它是减轻COVID-19中器官损伤的潜在治疗标.
- EAS1-ACE2轴在亡中的作用需要在涉及缺氧和细胞因子信号传递的非病毒病理背景下进一步研究.
相关概念视频
02:39lncRNA - Long Non-coding RNAs
9.8K
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...
9.8K
02:39lncRNA - Long Non-coding RNAs
3.5K
3.5K
01:20Types of RNA
9.0K
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...
9.0K
01:23Types of RNA
72.5K
Overview
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 the regulation of 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...
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 the regulation of 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...
72.5K
02:30siRNA - Small Interfering RNAs
18.4K
Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
18.4K
02:15Experimental RNAi
7.3K
RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
7.3K