在未折叠的蛋白质反应过程中,内质网膜局部化的mRNAs的衰变
Julie Hollien1, Jonathan S Weissman
1Department of Cellular and Molecular Pharmacology, University of California San Francisco, Howard Hughes Medical Institute, San Francisco, CA 94143, USA.
Science (New York, N.Y.)
|July 11, 2006
概括
展开的蛋白质反应 (UPR) 使用需要内醇的酶-1 (IRE1) 来降解特定的mRNA. 这一过程有助于内质网膜 (ER) 从错误折叠的蛋白质中恢复,通过停止具有挑战性的蛋白质生产.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 展开的蛋白质反应 (UPR) 是一种细胞通路,有助于内分泌网膜 (ER) 应对错误折叠的蛋白质带来的压力.
- 需要内醇的酶-1 (IRE1) 是UPR中的一个关键传感器,已知可以通过mRNA裂变激活转录因子X盒结合蛋白1 (XBP1).
研究的目的:
- 调查IRE1为UPR做出贡献的新机制.
- 为了确定IRE1是否调解mRNA降解,而不依赖于其在XBP1激活中的作用.
主要方法:
- 对mRNA局部化到ER膜的分析.
- 通过IRE1.1对特定序列mRNA识别的研究.
- 评估IRE1介导的mRNA降解途径.
主要成果:
- IRE1独立调解特定mRNAs子集的快速降解.
- mRNA降解取决于ER膜局部和编码的氨基酸序列.
- 这种降解途径补充了现有的UPR机制.
结论:
- IRE1在选择性降解特定mRNA方面具有以前未知的功能.
- 这种IRE1介导的mRNA降解有助于在UPR期间的ER重塑.
- 这些发现为IRE1在细胞应激反应中的多方面的作用提供了新的见解.
相关概念视频
02:31Nuclear 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...
02:27Nonsense-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,...
02:51mRNA 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
02:31Nuclear 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...
02:27Nonsense-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,...
02:51mRNA 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