lncRNAs通过通过Alu元素与3' UTRs重复通过STAU1介导的mRNA衰变进行交换
Chenguang Gong1, Lynne E Maquat
1Department of Biochemistry and Biophysics, School of Medicine and Dentistry, University of Rochester, Rochester, New York 14642, USA.
Nature
|February 11, 2011
概括
长非编码RNAs (lncRNAs) 可以通过与Staufen 1 (STAU1) 结合来调解mRNA衰变. 这种由Alu元素促进的相互作用揭示了基因调节和RNA衰变途径的新机制.
科学领域:
- 分子生物学分子生物学
- 在RNA生物学,RNA生物学.
- 基因规则 基因规则
背景情况:
- 阶段1 (STAU1) 介导的信使RNA衰变 (SMD) 针对的是翻译活性mRNAs.
- 之前在ARF1mRNA中发现的STAU1结合部位具有特定的结构特征.
- 在其他中小企业目标中没有发现类似的结构,这表明对理解的差距.
研究的目的:
- 阐明STAU1与其他mRNA标结合的机制.
- 研究SMD中非编码RNA和Alu元素的作用.
- 在基因调节中识别 lncRNAs 的新功能.
主要方法:
- 在mRNA 3' UTRs中分析STAU1结合位点.
- 研究mRNA和lncRNA中的Alu元素之间的相互作用.
- 评估lncRNAs对mRNA衰变速率的影响.
主要成果:
- 通过mRNA 3' UTRs和lncRNAs中的Alu元素之间的基配对,可以形成STAU1结合位.
- 一个单一的lncRNA可以调节多个SMD目标.
- 不同的lncRNA可以准相同的mRNA.
- 并非所有含有 Alu 元素的 mRNA 都是 SMD 的目标.
结论:
- lncRNAs可以通过将STAU1招募到特定的mRNAs来作为跨作用RNA效应器发挥作用.
- 这种相互作用调解了mRNA衰变,这是 lncRNAs 和 Alu 元素的以前不被重视的功能.
- 这些lncRNA被命名为半STAU1结合位点RNAs (1/2-sbsRNAs).
相关概念视频
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,...
02:27Nonsense-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
02:51mRNA 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
02:39lncRNA - Long Non-coding RNAs
In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA (lncRNA)...
02:39lncRNA - Long Non-coding RNAs
In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA (lncRNA)...