艾滋病毒-1A环和tRNA的RNA复合体(Lys,3) 通过核酸修饰来稳定
Ashok C Bajji1, Mallikarjun Sundaram, David G Myszka
1Department of Medicinal Chemistry, 30 South 2000 East Room 307, University of Utah, Salt Lake City, Utah 84112, USA.
Journal of the American Chemical Society
|November 28, 2002
概括
转移RNA (tRNA) 中的超变核酸在抗干环 (ASLs) 中稳定了HIV转录启动复合体内的关键RNA-RNA相互作用. 这些修改对于形成稳定的复合体至关重要,影响HIV复制.
科学领域:
- 分子生物学分子生物学
- 病毒学 病毒学
- 生物化学 生物化学
背景情况:
- 人类免疫缺陷病毒 (HIV) 转录启动综合体需要特定的RNA-RNA相互作用.
- 一个关键的相互作用涉及到原始tRNA抗和HIV基因组中保存的A丰富循环.
- 对于tRNA修饰在稳定该复合体中的作用尚未完全理解.
研究的目的:
- 调查tRNA抗干环 (ASLs) 中超改性核酸在稳定与HIV转录相关的RNA-RNA相互作用中的作用.
- 确定来自细菌和哺乳动物来源的特定tRNA修改对复杂稳定性的贡献.
主要方法:
- 使用表面等离子体共振 (SPR) 来量化tRNA ASL发针与A循环发针模型的结合亲和力.
- 实验使用了tRNA ASLs,其中包括来自*Escherichia coli* tRNALys和人类tRNALys的修改,3.
- 对完全和部分修改的tRNAASL进行了亲和度测量.
主要成果:
- 在tRNA ASLs中的过度修饰的核酸显著稳定RNA-RNA相互作用在抗/A循环复合模型中.
- 大肠杆菌tRNALys和人类tRNALys,3 ASL头发针都与A环头发针形成了稳定的复合体.
- 部分修改的tRNA ASLs表现出较低的结合亲和力,表明细菌和哺乳动物tRNA修改对复杂稳定有明显的贡献.
结论:
- 在tRNA ASL中,超改性核酸在稳定HIV转录启动复合体所必需的RNA-RNA相互作用方面发挥着至关重要的作用.
- 这些发现支持对抗/A循环复合体的互补RNA相互作用模型,类似于tRNAAsp.
- 了解这些稳定机制为抗病毒疗法提供了潜在的点.
相关概念视频
RNA Structure
Overview
The basic structure of RNA consists of a five-carbon sugar and one of four nitrogenous bases. Although most RNA is single-stranded, it can form complex secondary and tertiary structures. Such structures play essential roles in the regulation of transcription and translation.
Different Types of RNA Have the Same Basic Structure
There are three main types of ribonucleic acid (RNA): messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). All three RNA types consist of a...
The basic structure of RNA consists of a five-carbon sugar and one of four nitrogenous bases. Although most RNA is single-stranded, it can form complex secondary and tertiary structures. Such structures play essential roles in the regulation of transcription and translation.
Different Types of RNA Have the Same Basic Structure
There are three main types of ribonucleic acid (RNA): messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). All three RNA types consist of a...
Transfer RNA Synthesis
One of the unique features of tRNA is the presence of modified bases. In some tRNAs, modified bases account for nearly 20% of the total bases in the molecule. Altogether, these unusual bases protect the tRNA from enzymatic degradation by RNases.
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
Leaky Scanning
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 stands for...
RNA Structure
The basic structure of RNA consists of a string of ribonucleotides attached by phosphodiester bonds. Although most RNA is single-stranded, it can form complex secondary and tertiary structures. Such structures play essential roles in the regulation of transcription and translation.
Different Types of RNA Have the Same Basic Structure
There are three main types of ribonucleic acid (RNA) involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). All three...
Different Types of RNA Have the Same Basic Structure
There are three main types of ribonucleic acid (RNA) involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). All three...
Transfer RNA Synthesis
One of the unique features of tRNA is the presence of modified bases. In some tRNAs, modified bases account for nearly 20% of the total bases in the molecule. Altogether, these unusual bases protect the tRNA from enzymatic degradation by RNases.
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
Nucleic Acid Structure
The pentose sugar in DNA is deoxyribose, while in RNA the pentose sugar is ribose. The difference between the sugars is the presence of the hydroxyl group on the ribose's second carbon and a hydrogen on the deoxyribose's second carbon. The phosphate residue attaches to the hydroxyl group of the 5′ carbon of one sugar and the hydroxyl group of the 3′ carbon of the sugar of the next nucleotide, which forms a 5′ to 3′ phosphodiester linkage.
DNA Structure
DNA has a double-helix structure. The...
DNA Structure
DNA has a double-helix structure. The...


