通过热冲击-乌比奎丁-蛋白酶体通路控制mRNA衰变
1Department of Microbiology and Biochemistry, New York University School of Medicine, New York, NY 10016, USA.
概括
富含AU的mRNA衰变是由AUF1蛋白结合来调节的. 热冲击蛋白70 (hsp70) 扣留AUF1,阻断mRNA降解并将其连接到无素-蛋白酶体通路.
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:
- 细胞因子和原瘤基因信使RNA (mRNA) 在它们的3'未翻译区域中含有富含AU元素 (AREs),以快速降解为目标.
- 富含AU结合蛋白AUF1 (AUF1) 在这种衰变过程中起着至关重要的作用,与其他蛋白质相互作用,如热冲击蛋白 (hsc70-hsp70) 和翻译启动因子eIF4G.
研究的目的:
- 阐明了AU丰富的mRNA衰变背后的分子机制.
- 研究AUF1蛋白的作用及其对mRNA稳定性的相互作用.
- 为了确定mRNA降解与泛素-蛋白酶体通路之间的联系.
主要方法:
- 研究了AUF1与hsc70-hsp70,eIF4G和多A结合蛋白的复杂形成.
- 分析了AU丰富的mRNA衰变与eIF4G从AUF1.1的移位之间的关联.
- 检查了AUF1.1的无处化和蛋白质体降解.
- 研究了热冲击诱导的hsp70,ubiquitin-proteasome网络下调和E1酶失活对AUF1局部化和mRNA衰变的影响.
主要成果:
- 富含AU的mRNA衰变涉及AUF1复杂化与hsc70-hsp70,eIF4G和多A结合蛋白.
- 衰变过程与eIF4G从AUF1的移位,随后的AUF1无化和蛋白质体降解有关.
- 诱导hsp70,抑制乌比基蛋白酶系统,或非激活E1酶导致hsp70介导的AUF1在周核核中的封存.
- 这种隔离有效地阻止了富含AU的mRNA的衰变和AUF1蛋白的降解.
结论:
- 细胞因子mRNAs的快速降解与无素-蛋白酶体通路直接相关.
- 热冲击蛋白70在调节AUF1稳定性和AU丰富的mRNA衰变方面发挥着至关重要的作用.
- AUF1蛋白的稳定性和定位是控制特定mRNA群体的周转的关键决定因素.
相关概念视频
Nuclear Export of mRNA
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...
Regulation of Expression Occurs at Multiple Steps
Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
mRNA Stability and Gene Expression
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
Nuclear Export of mRNA
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...
mRNA Stability and Gene Expression
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
Regulation of Expression at Multiple Steps
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 addition of a...


