EDC4-XRN1相互作用控制P体动态,将mRNA分解与衰变联系起来
William R Brothers1, Farah Ali1, Sam Kajjo1
1Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC, Canada.
The EMBO journal
|August 25, 2023
概括
XRN1和EDC4蛋白之间的相互作用调节mRNA分解和衰变. 破坏这种相互作用会导致更大的处理体 (P体),防止mRNA衰变,影响细胞活力.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 死亡化依赖的mRNA脱落和衰变是细胞质mRNA循环的主要途径.
- 包括DCP2和XRN1在内的mRNA衰变因子与EDC4等蛋白质相关联,这是一种增强脱落的支架.
- 处理体 (P体) 是参与mRNA衰变的核糖蛋白颗粒,但对其不至关重要.
研究的目的:
- 研究EDC4-XRN1相互作用在调节mRNA脱落和衰变中的作用.
- 确定破坏EDC4-XRN1相互作用对P体动态和mRNA稳定性的影响.
- 阐明P体在细胞过程中的功能,特别是在有限的XRN1.1条件下.
主要方法:
- 干扰EDC4-XRN1相互作用并改变它们的静态度.
- 对mRNA分离率和微RNA向的mRNA稳定性的分析.
- 用显微镜评估P体的大小和动态.
- 评估细胞活力和压力颗粒的形成.
主要成果:
- 破坏EDC4-XRN1相互作用或改变静态度会抑制mRNA脱落.
- 微RNA向的mRNA在EDC4-XRN1相互作用中断时稳定在一个翻译抑制状态.
- 抑制分离导致扩大的P体,这些P体可以积极阻止mRNA分离.
- 当XRN1受限时,P体对细胞活力至关重要,并防止应力颗粒形成.
结论:
- 在人体细胞中,XRN1和EDC4之间的相互作用对于协调mRNA分解与5'-3'衰变至关重要.
- P体动力学由EDC4-XRN1相互作用调节,影响mRNA周转.
- P体在维持细胞平衡中起着至关重要的作用,特别是在涉及有限XRN1.1的压力条件下.
更多相关视频
09:26Identification of Footprints of RNA:Protein Complexes via RNA Immunoprecipitation in Tandem Followed by Sequencing RIPiT-Seq
Published on: July 10, 2019
10.6K
09:16Analysis of RNA Processing Reactions Using Cell Free Systems: 3' End Cleavage of Pre-mRNA Substrates in vitro
Published on: May 3, 2014
12.9K
相关概念视频
Nonsense-mediated mRNA Decay
10.7K
The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
10.7K
mRNA Stability and Gene Expression
5.6K
The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
Cis-acting Elements involved in mRNA stability
Cis-acting Elements involved in mRNA stability
5.6K
Nuclear Export of mRNA
7.7K
Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
7.7K
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
RNA Editing
9.0K
RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...
9.0K
RNA Stability
33.6K
Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
33.6K
