干环结合蛋白促进SARS-CoV-2复制通过-1编程的核糖体框架转移
Tanxiu Chen1,2,3, Ruimin Zhu1, Tingfu Du2
1State Key Laboratory of Respiratory Health and Multimorbidity, National Center of Technology Innovation for Animal Model, Key Laboratory of Pathogen Infection Prevention and Control (Peking Union Medical College), Ministry of Education, Institute of Laboratory Animal Science, CAMS & PUMC, Beijing, China.
Signal transduction and targeted therapy
|June 13, 2025
概括
干环结合蛋白 (SLBP) 促进SARS-CoV-2的框架转移,这是一个关键的病毒过程. 这一发现确定了SLBP作为COVID-19治疗的潜在治疗标.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 宿主-病原体相互作用
背景情况:
- 严重急性呼吸道综合征冠状病毒2 (SARS-CoV-2) 依赖于-1编程的核糖体框架转移 (-1 PRF) 进行多蛋白质合成.
- 调节SARS-CoV-2 -1 PRF的宿主因素在很大程度上仍未确定,限制了治疗策略.
研究的目的:
- 为了识别与SARS-CoV-2 -1 PRF RNA相互作用的宿主蛋白质.
- 研究已识别的宿主蛋白在病毒复制和框架转移中的作用.
- 探索COVID-19的潜在治疗点.
主要方法:
- RNA拉下测试与质谱学相结合,以确定相互作用的主体蛋白质.
- 深度学习预测 (PrismNet) 对于RNA与蛋白质结合的概率.
- 电泳运动移位测试 (EMSA) 和RNA拉下测试以确认直接结合.
- 小光显微镜在现场杂交 (smFISH) 用于定位化研究.
- 在体外翻译系统以评估移效率.
主要成果:
- 确定了五种宿主蛋白质,包括干环结合蛋白 (SLBP),与-1 PRF RNA相互作用.
- SLBP直接与SARS-CoV-2 -1 PRF RNA结合,特别是在干环3区域.
- 过度表达SLBP增强-1PRF并促进病毒复制.
- SLBP影响其他宿主因子 (FUBP3,RPS3A,RPL10A) 与-1 PRF RNA区域的结合.
结论:
- 干环结合蛋白 (SLBP) 是一种促进SARS-CoV-2 -1 PRF的新型宿主因子.
- SLBP与病毒RNA的相互作用对于有效的病毒复制至关重要.
- SLBP代表了开发新型COVID-19治疗方法的潜在可用药物标.
相关概念视频
Leaky Scanning
5.1K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.1K
Riboswitches
8.1K
Riboswitches are non-coding mRNA domains that regulate the transcription and translation of downstream genes without the help of proteins. Riboswitches bind directly to a metabolite and can form unique stem-loop or hairpin structures in response to the amount of the metabolite present. They have two distinct regions – a metabolite-binding aptamer and an expression platform.
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
8.1K
Types of RNA
63.4K
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...
63.4K
Initiation of Translation
31.9K
Initiating translation is complex because it involves multiple molecules. Initiator tRNA, ribosomal subunits, and eukaryotic initiation factors (eIFs) are all required to assemble on the initiation codon of mRNA. This process consists of several steps that are mediated by different eIFs.
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...
31.9K
Bacterial RNA Polymerase
29.4K
Unlike eukaryotes, bacteria use a single RNA Polymerase (RNAP) to transcribe all genes. The different subunits of bacterial RNAPhave distinct functions. The multisubunit structure of the bacterial RNAP helps the enzyme to maintain catalytic function, facilitate assembly, interact with DNA and RNA, and self-regulate its activity.
In most genes, the transcription site is a single base present upstream of the coding sequence. Though RNAP is a catalytically efficient enzyme, it does not recognize...
In most genes, the transcription site is a single base present upstream of the coding sequence. Though RNAP is a catalytically efficient enzyme, it does not recognize...
29.4K
Nonsense-mediated mRNA Decay
2.8K
2.8K


