人类Upf蛋白针对mRNA进行无意中介衰变,当它们与终结子的下游结合时
J Lykke-Andersen1, M D Shu, J A Steitz
1Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06536, USA.
Cell
|February 13, 2001
概括
无意中介衰变 (NMD) 消除了有缺陷的mRNAs. 新型人类蛋白质hUpf2,hUpf3a和hUpf3b以及hUpf1形成了一个动态复合体,该复合体始于细胞核,并在细胞质中触发NMD.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 遗传学 是一个遗传学.
背景情况:
- 无意中介衰变 (NMD) 是一个关键的细胞监测途径.
- NMD消除了含有过早终止子 (PTC) 的真核信使RNA (mRNA).
- 区分PTC与真正的停止编码子依赖于cis作用元素,特别是exon-exon连接.
研究的目的:
- 识别和描述参与NMD途径的新型人类蛋白质.
- 阐明这些新发现的NMD因子的细胞局部化和相互作用.
- 研究这些蛋白质对NMD启动和执行的机制.
主要方法:
- 同免疫沉测试检测HeLa细胞提取物中的蛋白质复合物.
- 在完整的细胞中使用免疫光的亚细胞局部化研究.
- 在体内分析蛋白质与拼接β-环球蛋白mRNA的关联.
- 功能性试验涉及hUpf蛋白与β-环球蛋白mRNA的3'未翻译区域 (UTR) 的结合.
主要成果:
- 鉴定了三种人类新型NMD蛋白:hUpf2,hUpf3a和hUpf3b.
- 在细胞提取物中,这些蛋白质与hUpf1.1形成复合体.
- 在完整的细胞中,hUpf3a和hUpf3b表现出核细胞质的穿,hUpf2是周核的,hUpf1是细胞质的.
- hUpf3a和hUpf3b选择性地与拼接的β-全球蛋白mRNA结合在一起.
- 将任何hUpf蛋白与β-环球蛋白mRNA 3'UTR结合起来,就会触发NMD.
结论:
- 一个动态的hUpf复合体,包括hUpf1,hUpf2,hUpf3a和hUpf3b,在NMD中发挥着核心作用.
- 复杂的组合开始于核中的mRNA外子-外子结点.
- 该复合体在细胞质中触发NMD,在识别下游的翻译终端站点时.
- 这些发现为真核细胞mRNA监测的分子机制提供了新的见解.
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...
Nonsense-mediated mRNA Decay
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,...
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...
Nonsense-mediated mRNA Decay
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,...
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


