细胞活性N6-甲基氨酸RNA脱甲基酶FTO抑制剂的发展
1State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Journal of the American Chemical Society
|October 11, 2012
概括
科学家们发现了抑制FTO酶的小分子,该酶调节RNA的N(6) - 甲基氨酸 (m(6) A水平. 自然化合物莱因是一种强大的FTO抑制剂,为RNA生物学和药物发现提供了新的工具.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 药物发现 药物发现 药物发现
背景情况:
- FTO (FTO) 酶是一种二氧化原酶,可以从RNA中去除N(6) -甲基氨酸 (m(6) A) 修饰物.
- FTO在哺乳动物基因调节中发挥着重要作用,是第一个被确定的RNA脱甲基酶.
- m(6) 一种修饰对于各种RNA功能和细胞过程至关重要.
研究的目的:
- 为了确定人类FTO脱甲基酶的小分子抑制剂.
- 探索针对FTO活动的潜在治疗剂.
- 开发用于研究RNA生物学的新型化学探针.
主要方法:
- 基于结构的虚拟选被用于识别潜在的FTO抑制剂.
- 进行生物化学分析以验证抑制剂活性.
- 实验室和细胞测试用于评估已识别的化合物的疗效.
主要成果:
- 确定了几种人类FTO脱甲基酶的小分子抑制剂.
- 自然产品莱因成为最强大的抑制剂.
- 莱具有竞争性地与FTO活性部位结合,并抑制细胞中的m(6) A脱甲基化.
结论:
- 莱因和其他FTO抑制剂的发现为RNA生物学研究提供了宝贵的工具.
- 这些发现为开发针对RNA修饰途径的新疗法开辟了道路.
- 这项研究推进了针对RNA相关疾病的药物发现领域.
相关概念视频
Experimental RNAi
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...
RNA Interference
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...
RNA Interference
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...
Eukaryotic Transcription Inhibitors
Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a DNA...
Eukaryotic transcription inhibitors usually contain two distinct domains, a DNA...
MicroRNAs
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 the pre-miRNA...


