通过综合性微RNA网络分析发现超增强器介导的RNA处理
Hiroshi I Suzuki1, Richard A Young2, Phillip A Sharp3
1David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Cell
|March 12, 2017
概括
超级增强剂通过增强转录和处理来驱动主微RNA (miRNA) 的产生. 这些调节区域也影响miRNA网络,并与癌症特征有关.
科学领域:
- 基因组学
- 分子生物学
- 表观遗传学
背景情况:
- 超级增强剂是控制细胞身份和疾病基因的关键调控元素.
- 超级增强剂在微RNA (miRNA) 网络中的确切作用在很大程度上是未知的.
研究的目的:
- 研究超级增强剂在miRNA生物生成中的功能及其对细胞身份和疾病的影响.
- 阐明超增强剂调节miRNA转录和处理的机制.
主要方法:
- 通过CRISPR/Cas9基因组编辑分析超级增强器功能.
- 分析H3K4me3域及其与miRNA表达的相关性.
- 用BET- 代蛋白抑制剂JQ1治疗,以评估对超级增强剂活性的影响.
- 研究超级增强剂,DGCR8/Drosha复合物和mRNA稳定性的相互作用.
主要成果:
- 超级增强剂增强了主要miRNAs (pri- miRNAs) 的转录和Drosha/ DGCR8介导的处理.
- 超级增强剂与H3K4me3域一起建立了组织特异和保存的miRNA表达图谱.
- 超级增强剂成分合作招募Drosha/DGCR8,促进miRNA的产生.
- 超级增强剂与DGCR8/Drosha相互作用,并调节mRNA稳定性,表明新的RNA处理作用.
- 超级增强剂与涉及癌症特征的miRNA相关.
结论:
- 超级增强剂在miRNA生物发生过程中起着至关重要的作用,影响细胞身份和疾病途径.
- 这项研究揭示了超级增强剂在超出转录控制的RNA处理中的未知的功能.
- 超级增强剂在miRNA生物学中代表着重要的调节层,对了解健康和疾病有影响.
相关概念视频
MicroRNAs
4.2K
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...
4.2K
MicroRNAs
24.4K
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...
24.4K
Chromatin Structure Regulates pre-mRNA Processing
8.4K
In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
The chromatin structure, especially...
8.4K
siRNA - Small Interfering RNAs
18.9K
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...
18.9K
Experimental RNAi
8.1K
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...
8.1K
RNA Interference
28.4K
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...
28.4K


