一个假的3'-UTR促进异常终结,并触发无意义介导的mRNA衰变
Nadia Amrani1, Robin Ganesan, Stephanie Kervestin
1Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, Massachusetts 01655-0122, USA.
Nature
|November 5, 2004
概括
无意中介衰变 (NMD) 是由过早的翻译终止引发的. 在过早停止子时异常的核糖体行为,取决于3'-UTR配置,影响mRNA稳定性.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 在RNA生物学,RNA生物学.
背景情况:
- 无意中介的信使RNA衰变 (NMD) 消除了异常的转录.
- 区分过早翻译和正常翻译终止的确切机制尚不清楚.
- 目前的模型争论是否衰变因子或终止异常引发NMD.
研究的目的:
- 为了研究核糖体行为在早期终止的代.
- 阐明3个未翻译区域 (UTR) 在NMD监管中的作用.
- 了解mRNA监控的分子基础.
主要方法:
- Primer 延伸抑制 (脚印) 试验用于映射核糖体位置.
- 对具有和没有关键NMD因子 (Upf1p) 的酵母提取物的分析.
- 使用绑定聚A结合蛋白 (Pab1p) 模拟3 -UTR功能的实验.
主要成果:
- 过早终结的编码子 (UAA,UGA) 在酵母提取物中导致核糖体停滞和上游迁移.
- 这种异常的核糖体行为取决于无意义的密码子识别.
- 通过去除NMD因子Upf1p或提供功能性3-UTR模仿 (Pab1p) 来解决异常.
结论:
- 过早的翻译终止本质上是异常的.
- 有效的终结和mRNA稳定性依赖于适当的3-UTR配置.
- 3 -UTR在招募终结因子和稳定转录中发挥着关键作用.
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