蛋白质和RNA区域的剖析是SPEN与XIST A重复RNA结合所需的
Aileen C Button1, Simone D Hall1, Ethan L Ashley1
1Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, California 92093, USA.
概括
XIST RNA和SPEN蛋白的相互作用启动了X染色体的沉默. 特定的RNA结构和蛋白质区域对于这种高亲和度结合至关重要,揭示了关键的分子机制.
科学领域:
- 表观遗传学和基因调控
- 在RNA生物学,RNA生物学.
- 分子遗传学 分子遗传学
背景情况:
- 在雌性哺乳动物中,XIST非编码RNA启动X染色体沉默.
- SPEN蛋白 (也称为SHARP或MINT) 是由XISTRNA招募的.
- 在SPEN中,N-CoR2和HDAC3被用于诱导激素脱甲基化和基因沉默.
研究的目的:
- 为了在体外研究XIST-SPEN复合体形成的分子基础.
- 为了确定XIST-SPEN结合的序列和结构决定因素.
- 了解RNA结构在X染色体沉默启动中的作用.
主要方法:
- 在体外结合测试中使用截断的XISTRNA和SPEN蛋白质变体.
- 对XISTRNA的化学结构进行探测.
- 对RNA-蛋白相互作用的计算建模.
主要成果:
- SPEN 蛋白质的 RRM 4 域对于 XIST RNA 结合至关重要.
- 高亲和度结合需要XISTRNA的至少四个A重复段.
- 特定的RNA结构图案,包括与未配对的腺素相互重复的重复,与SPEN结合相关.
结论:
- 确定了XIST-SPEN相互作用的新序列和结构决定因素.
- 这些发现阐明了 X 染色体沉默启动背后的分子机制.
- 该研究提供了对精确的RNA结构的洞察,这些结构有助于SPEN的招聘.
相关概念视频
RNA Splicing
56.4K
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...
56.4K
Inheritance of Chromatin Structures
6.3K
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...
6.3K
Chromatin Structure Regulates pre-mRNA Processing
7.0K
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...
7.0K
Alternative RNA Splicing
21.2K
Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
21.2K
Chromatin Structure and RNA Splicing
2.7K
2.7K
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


