一个蛋白质组合介导Xist定位和基因沉默
Amy Pandya-Jones1, Yolanda Markaki1,2, Jacques Serizay1,3,4
1Department of Biological Chemistry at the David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Nature
|September 10, 2020
概括
长非编码RNA Xist 种植了一种对X染色体失活 (XCI) 和遗传基因沉默至关重要的蛋白质凝聚物,过渡到Xist独立阶段.
科学领域:
- 分子生物学
- 表观遗传学
- 基因组学
背景情况:
- 核区通过不太了解的分子力量调节基因表达.
- 长非编码RNA Xist招募蛋白质形成一个X染色体失活区 (XCI).
- 不活跃的X (Xi) 分区过渡到一个稳定的,Xist独立的状态.
研究的目的:
- 调查基因间隔形成和遗传基因沉默的分子机制.
- 确定驱动Xi区间稳定性的蛋白质组成部分和力量.
- 了解发展转向XIS独立的XCI.
主要方法:
- 用于研究蛋白质-RNA相互作用的生物化学测试.
- 细胞成像可视化隔间的形成和动态.
- 基因操纵以评估XCI中发现的蛋白质的功能.
主要成果:
- 在Xist的E重复元件上组装Xist的RNA结合蛋白 (PTBP1,MATR3,TDP-43,CELF1).
- 这些蛋白质形成了自我聚合的凝聚物,对基因沉默和Xist定至关重要.
- 凝结物独立于Xist维持基因沉默,对于Xist独立的XCI阶段至关重要.
结论:
- 通过播种无处不在的RNA结合蛋白的凝聚物,Xist启动了Xi区.
- 这种凝聚物驱动了遗传性基因沉默,并成为XIS独立XCI的基础.
- 通过RNA模板蛋白质聚合揭示了表观遗传记忆的新机制.
更多相关视频
08:27A Non-random Mouse Model for Pharmacological Reactivation of Mecp2 on the Inactive X Chromosome
Published on: May 22, 2019
6.6K
15:54Combined DNA-RNA Fluorescent In situ Hybridization FISH to Study X Chromosome Inactivation in Differentiated Female Mouse Embryonic Stem Cells
Published on: June 14, 2014
28.2K
相关概念视频
Inheritance of Chromatin Structures
7.1K
Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
7.1K
X-Inactivation
40.9K
The human X chromosome contains over ten times the number of genes as in the Y chromosome. Since males have only one X chromosome, and females have two, one might expect females to produce twice as many of the proteins, with undesirable results.
40.9K
siRNA - Small Interfering RNAs
18.0K
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...
18.0K
Experimental RNAi
7.0K
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...
7.0K
Chromatin Structure Regulates pre-mRNA Processing
7.9K
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...
7.9K
Epigenetic Regulation
33.0K
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
33.0K
