拼接因子CCAR1调节了Fanconi贫血/BRCA通路的发生
Naoya Harada1, Shuhei Asada1, Lige Jiang1
1Division of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
Molecular cell
|July 18, 2024
概括
细胞分裂周期和细胞亡调节器1 (CCAR1) 对于Fanconi贫血 (FA) 途径的功能至关重要. CCAR1调节FANCA mRNA剪接,确保正确的DNA修复蛋白质表达.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 细胞生物学 细胞生物学
背景情况:
- 芬科尼贫血 (FA) 途径蛋白修复DNA跨链交叉链 (ICLs).
- 细胞分裂周期和细胞亡调节器1 (CCAR1) 在FA/BRCA通路中的作用以前是未知的.
- 在保持基因组稳定性方面,ICL修复至关重要.
研究的目的:
- 为了研究CCAR1在FA/BRCA通路中的功能.
- 阐明CCAR1影响DNA修复的机制.
- 为了确定CCAR1是否影响FA蛋白的表达.
主要方法:
- 同免疫沉降测定检测蛋白质-RNA相互作用.
- 对mRNA处理和拼接的分析.
- 西方涂抹以评估蛋白质表达水平.
- 涉及CCAR1域的功能性测试.
主要成果:
- 在FA/BRCA通路中,CCAR1起着上游的作用.
- 在人类细胞中,CCAR1对于FANCA蛋白表达至关重要.
- CCAR1与FANCA前mRNA相互作用,并且对于其正确的处理是必要的.
- 失去CCAR1导致FANCA mRNA中保留毒素外子,从而降低蛋白质水平.
- CCAR1的EF手域是与结合体和毒素外子切除的相互作用所必需的.
结论:
- CCAR1作为一个拼接调节器,对于正常的FANCA mRNA拼接至关重要.
- 在剪接中CCAR1的功能影响FA/BRCA通路和DNA修复.
- CCAR1调节了参与各种细胞过程的其他mRNAs的表达.
相关概念视频
01:32RNA Splicing
56.3K
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...
56.3K
02:18Alternative RNA Splicing
21.1K
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...
21.1K
02:41Chromatin 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
02:37Restarting Stalled Replication Forks
5.8K
DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
5.8K
01:23Regulation of Expression at Multiple Steps
886
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
886
01:36Pre-mRNA Processing: RNA Splicing
5.2K
5.2K