无化SRp38作为应对热冲击的拼接抑制剂
Chanseok Shin1, Ying Feng, James L Manley
1Department of Biological Sciences, Columbia University, New York, New York 10027, USA.
Nature
|February 7, 2004
概括
热冲击通过SRp38蛋白质脱酸化抑制RNA剪接. 这种应激反应机制对于细胞生存至关重要,因为SRp38抑制了拼接机制.
科学领域:
- 分子生物学分子生物学
- 细胞应激反应的应激反应
- 基因表达规范 基因表达规范
背景情况:
- 细胞压力,就像热冲击一样,通过RNA剪接的变化改变基因表达.
- 在热冲击期间导致拼接抑制的具体因素尚未确定.
- 已知SRp38是一种SR蛋白,可以抑制拼接,并通过脱酸化激活.
研究的目的:
- 研究SRp38在热冲击诱导的拼接抑制中的作用.
- 阐明SRp38在细胞应激过程中抑制拼接的机制.
主要方法:
- 分析SRp38在热冲击反应中的脱化.
- 在细胞提取物中剥离SRp38,以评估其对剪接的影响.
- 用去酸化的SRp38.38,重建拼接抑制.
- 确定无化SRp38.38的蛋白相互作用.
- 检查SRp38缺乏细胞中的细胞循环概况和应力恢复.
主要成果:
- 在热冲击期间,SRp38脱化与拼接抑制相关.
- 在热冲击细胞提取物中,SRp38的耗尽抑制了拼接.
- 无化SRp38通过干扰U1 snRNP 5'-splice-site识别来抑制拼接.
- 缺少SRp38的细胞表现出线索性缺陷,以及受热冲击后恢复能力受损.
结论:
- 在热应力下,SRp38是剪接抑制的关键调节器.
- 脱化SRp38通过破坏spliceosome组装来抑制拼接.
- SRp38对于细胞生存和应激适应至关重要.
相关概念视频
Directing Proteins to the Rough Endoplasmic Reticulum
12.1K
The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
12.1K
Single-Strand DNA Binding Proteins
12.9K
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...
12.9K
Regulation of the Unfolded Protein Response
2.2K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.2K
Translational Regulation
893
Translational regulation in prokaryotes ensures efficient protein synthesis by controlling ribosome access to mRNA. This regulation is mediated by secondary RNA structures, including translational riboswitches, RNA thermometers, and small RNAs (sRNAs), which respond to intracellular and environmental signals to modulate gene expression.Translational RiboswitchesRiboswitches in the leader region of mRNAs can regulate translation by altering the accessibility of the Shine-Dalgarno (SD) sequence,...
893
Stringent Response in E. coli
533
Bacterial growth is closely tied to nutrient availability, with cells proliferating exponentially under favorable conditions and entering a stationary phase when resources become scarce. This transition is mediated by a regulatory mechanism known as the stringent response, which allows bacteria to adapt to nutrient deprivation by modulating gene expression and metabolic activity.During nutrient scarcity, intracellular amino acid levels decline. It results in the accumulation of uncharged tRNAs...
533
Other Stress Responses in Bacteria
593
Bacteria have global regulatory systems that control several types of stress mechanisms. These include Pho regulon and the heat shock response, which are essential systems for environmental adaptation, such as nutrient limitation and proteotoxic stress. The Pho regulon and the heat shock response exemplify bacterial resilience, enabling rapid adaptation to fluctuating environmental conditions.Pho RegulonBacteria require phosphorus for essential cellular processes, including nucleic acid...
593


