人类AGO2对指导RNA的5'-核酸基特异性识别的结构基础
Filipp Frank1, Nahum Sonenberg, Bhushan Nagar
1Department of Biochemistry, McGill University, Montréal, Québec H3G 0B1, Canada.
Nature
|May 28, 2010
概括
人类阿尔戈诺特蛋白 (AGOs) 在微RNA (miRNA) 的5'端对 uracil (U) 或腺因 (A) 显示出偏好. 结构研究揭示了AGO MID域内的特定相互作用,解释了这种核酸偏差,对基因调节至关重要.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 遗传学 是一个遗传学.
背景情况:
- 微RNAs (miRNAs) 通过与阿尔戈诺特蛋白 (AGOs) 相互作用来调节基因表达后转录.
- 以前对 prokaryotic AGOs 的研究表明,MID 域与 miRNA 5' 端的相互作用是核酸独立的.
- 细胞的miRNA序列和实验表明,在5'位置偏好 uracil (U) 或 adenine (A).
研究的目的:
- 确定真核RNA5'末端核酸偏好的结构基础.
- 为了研究人类AGO2的MID域与miRNA模拟的5'末端之间的相互作用.
主要方法:
- 人类AGO2 MID域的X射线晶体学复合与核酸单酸盐 (AMP,CMP,GMP,UMP).
- 核磁共振定位实验以确定结合亲缘关系.
主要成果:
- 晶体结构揭示了MID域的刚性循环和 uracil 单酸盐 (UMP) 或腺因单酸盐 (AMP) 之间的特定接触.
- 在MID域结构中,可以区分细胞氨酸单酸盐 (CMP) 和关氨酸单酸盐 (GMP).
- 结合性亲和度测量证实与CMP和GMP相比,AMP和UMP的亲和度更高.
结论:
- 结构证据支持在真核细胞AGO蛋白的MID域中的核酸特异相互作用.
- 这种特异性解释了在microRNAs的5'端观察到的U或A偏差,影响基因调节.
相关概念视频
01:23RNA 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...
01:23RNA 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...
02:36Transfer 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...
02:23RNA Editing
RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...
01:19RNA 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...
01:25Nucleic 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...