核酶对RNA的小分子向招募
Matthew G Costales1, Yasumasa Matsumoto1, Sai Pradeep Velagapudi1
1The Department of Chemistry , The Scripps Research Institute , Jupiter , Florida 33458 , United States.
Journal of the American Chemical Society
|May 25, 2018
概括
科学家们开发出一种能够在乳腺癌细胞中破坏致癌微RNA-96 (miR-96) 的小分子. 这种方法通过招募核酶来选择性地触发癌细胞的亡.
科学领域:
- 分子生物学
- 生物化学
- 抗癌药物
背景情况:
- RNA合成和降解是重要的生物过程.
- 像CRISPR这样的工程系统针对特定的RNA.
- 向致癌微RNAs (miRNAs) 是癌症治疗的一种策略.
研究的目的:
- 用小分子展示一种选择性RNA降解的新方法.
- 研究小分子的潜力,以招募核酶进行向的RNA破坏.
- 在癌细胞中抑制瘤性微RNA-96 (miR-96).
主要方法:
- 一个小分子结合剂被设计为结合miR-96前体.
- 结合物被添加了一个2'-5'多核酸来招募核酶L (RNase L).
- 该系统的有效性在乳腺癌细胞中进行了测试,评估了miR-96裂变,FOXO1抑制和亡诱导.
主要成果:
- 小分子结合物选择性激活内源RNase L.
- 激活的RNase L在癌细胞中催化分裂了miR-96前体.
- 沉默miR-96导致了亲亡的FOXO1转录因子的减压.
- 在乳腺癌细胞中引发了亡,
结论:
- 小分子可以通过核酶招募被编程来选择性地分裂RNA.
- 这种方法提供了具有治疗潜力的向RNA破坏的新策略.
- 这些发现对开发新型RNA向疗法具有广泛的意义.
相关概念视频
Transfer RNA Synthesis
13.4K
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...
13.4K
RNA Stability
35.8K
Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
35.8K
RNA Structure
79.2K
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...
79.2K
RNA Interference
28.2K
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...
28.2K
RNA Splicing
60.7K
Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
60.7K
Types of RNA
73.0K
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...
73.0K


