关于SID-1对双链RNA识别和传输的结构见解.
Jiangtao Zhang1,2, Chunhua Zhan1, Junping Fan3
1College of Life Science and Technology, Key Laboratory of Molecular Biophysics of MOE, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Nature structural & molecular biology
|April 25, 2024
概括
科学家们揭示了SID-1的结构,SID-1是一种蛋白质,对RNA吸收和系统RNA干扰 (RNAi) 在C. elegans中至关重要. 这一发现解释了SID-1如何识别和导入双链RNA (dsRNA),推动了基于RNA的治疗开发.
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:
- 细胞RNA吸收对于RNA干扰 (RNAi) 和新疗法至关重要.
- 在C. elegans中,系统性RNAi依赖于SID-1介导的双链RNA (dsRNA) 运输.
- 通过SID-1进行dSRNA内部化的精确机制尚未完全理解.
研究的目的:
- 阐明SID-1对dsRNA识别和导入的结构基础.
- 研究SID-1的结构特征在dsRNA内部化中的作用.
- 为开发基于dsRNA的应用程序提供机制性见解.
主要方法:
- 电子显微镜 (cryo-EM) 用于确定SID-1,SID-1-dsRNA复合体和人类同类 (SIDT1,SIDT2) 的结构.
- 结构分析以确定dSRNA结合的分子决定因素.
- 体研究涉及删除细胞内循环,以评估dSRNA吸收和RNAi疗效.
主要成果:
- 确定了SID-1的高分辨率冷EM结构及其与dsRNA.complex的复合物.
- 在SID-1同类体中确定了保守的同位体结构,其中SID-1具有独特的dsRNA识别位点.
- 证明SID-1中改变细胞内循环会损害dSRNA吸收和系统性RNAi,这表明存在内细胞机制.
结论:
- SID-1的结构解释了其特定的识别和dSRNA的进口.
- 对SID-1功能的结构洞察力为基于RNA的增强疗法铺平了道路.
- 这些发现表明SID-1-介导的dsRNA内部化存在一个内细胞通路.
相关概念视频
siRNA - Small Interfering RNAs
16.7K
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...
16.7K
RNA Interference
26.0K
RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
26.0K
Single-Strand DNA Binding Proteins
14.1K
For successful DNA replication, the unwinding of double-stranded DNA must be accompanied by stabilization and protection of the separated single strands of the DNA. This crucial task is performed by single-strand DNA-binding (SSB) proteins. They bind to the DNA in a sequence-independent manner, which means that the nitrogenous bases of the DNA need not be present in a specific order for binding of SSB proteins to it. The binding of SSB proteins straightens single-stranded DNA (ssDNA) and makes...
14.1K
Experimental 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
piRNA - 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
RNA Structure
4.8K
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...
4.8K


