人类DICER的冷EM结构切割了前-miRNA基质
Hansol Lee1,2, Soung-Hun Roh1,2
1School of Biological Sciences, Seoul National University, Seoul, South Korea.
The FEBS journal
|December 28, 2023
概括
人类Dicer (hDICER) 结构与前-miRNA结合,揭示了它如何识别和切割基质. 关键剩余和域移动解释了hDICER的存在.
科学领域:
- 分子生物学分子生物学
- 生物化学 生化学
- 遗传学 是一个遗传学.
背景情况:
- 迪克 (核糖核酶III酶) 对于RNA干扰至关重要,它将双链RNA转化为小RNA.
- 人类Dicer (hDICER) 将前微RNA (miRNA) 处理成成熟的miRNA,这一机制尚未完全理解.
- 之前的研究集中在长期的dsRNA裂变上,不清楚miRNA前处理.
研究的目的:
- 为了阐明人类Dicer (hDICER) 预微RNA处理的机制.
- 使用冷电子显微镜呈现hDICER与前-miRNA结合的结构基础.
- 将最近的结构发现与之前的Dicer研究进行比较.
主要方法:
- 电子显微镜 (cryo-EM) 用于确定hDICER与前-miRNA结合的结构.
- 结构分析以识别涉及基质识别的域移动和关键残留.
- 将新结构与现有的Dicer结构数据进行比较.
主要成果:
- 该结构揭示了hDICER的酶和dsRNA结合域 (dsRBD) 中的域移动.
- 在hDICER的顶点域和dsRBD中的特定残留物识别了前-miRNA末端和裂解部位.
- 顶端域口袋和dsrbd中的正电荷残留物对于基质识别和裂变部位的确定至关重要.
结论:
- 该结构提供了关于hDICER如何结合和分裂前-miRNA的机制性见解.
- 了解hDICER的基质识别,可以突出显示 cis 作用元素在处理过程中的作用.
- 这些发现对于理解hDICER相关疾病有价值.
关键词:
这就是说,Dicer.GYM的动机是GYM的动机.这是一种RNA干扰.识别RNARNA的识别电子显微镜的冷电子显微镜dsRNA-结合域是什么? dsRNA-结合域是什么?长时间的dsRNA裂变.这是一个小RNARNA.核糖核酸酶III的使用方法小的干扰RNAs可以干扰.更多相关视频
09:25Do's and Don'ts of Cryo-electron Microscopy: A Primer on Sample Preparation and High Quality Data Collection for Macromolecular 3D Reconstruction
Published on: January 9, 2015
46.2K
09:16Manual Blot-and-Plunge Freezing of Biological Specimens for Single-Particle Cryogenic Electron Microscopy
Published on: February 7, 2022
6.4K
相关概念视频
01:28Cryo-electron Microscopy
3.3K
Conventional electron microscopy (EM) involves dehydration, fixation, and staining of biological samples, which distorts the native state of biological molecules and results in several artifacts. Also, the high-energy electron beam damages the sample and makes it difficult to obtain high-resolution images. These issues can be addressed using cryo-EM, which uses frozen samples and gentler electron beams. The technique was developed by Jacques Dubochet, Joachim Frank, and Richard Henderson, for...
3.3K
02:57piRNA - Piwi-interacting RNAs
6.9K
PIWI-interacting RNAs, or piRNAs, are the most abundant short non-coding RNAs. More than 20,000 genes have been found in humans that code for piRNAs while only 2000 genes have been found for miRNAs. piRNAs can act at the transcriptional and post-transcriptional levels and have a vital role in silencing transposable elements present in germ cells. They are also involved in epigenetic silencing and activation. Previously, they were thought to function only in germ cells but new evidence suggests...
6.9K
01:25Nucleic Acid Structure
6.1K
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...
DNA Structure
DNA...
6.1K
02:01pre-mRNA Processing
52.9K
In eukaryotic cells, transcripts made by RNA polymerase are modified and processed before exiting the nucleus. Unprocessed RNA is called precursor mRNA or pre-mRNA to distinguish it from mature mRNA.
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a “cap” to the 5’ end of the growing transcript. In this process, a 5’ phosphate is replaced by modified guanosine that has a methyl group attached to it (7-Methyl...
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a “cap” to the 5’ end of the growing transcript. In this process, a 5’ phosphate is replaced by modified guanosine that has a methyl group attached to it (7-Methyl...
52.9K
01:22MicroRNAs
21.3K
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...
21.3K
02:15Experimental RNAi
6.1K
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...
6.1K