一个表达的伪基因调节其同类编码基因的信使RNA稳定性
Shinji Hirotsune1, Noriyuki Yoshida, Amy Chen
1Division of Neuroscience, Research Center for Genomic Medicine, Saitama Medical School Yamane 1397-1, Hidaka City, Saitama 350-1241, Japan. shinjih@saitama-med.ac.jp
Nature
|May 2, 2003
概括
表达的伪基因可以调节基因功能. 这项研究表明,一种伪基因 (Makorin1-p1) 控制了信使RNA的稳定性,影响了小鼠的发育,并提供了对非编码RNA角色的见解.
科学领域:
- 遗传学 遗传学 是一个
- 分子生物学分子生物学
- 发育生物学 发展生物学
背景情况:
- 伪基因是缺乏蛋白质功能的基因副本,其生物作用基本上未知.
- 人类基因组包含大约2万个伪基因,代表了基因组的很大一部分.
- 了解伪基因的功能对于理解基因组复杂性和基因调节至关重要.
研究的目的:
- 研究表达伪基因Makorin1-p1在调节基因表达中的功能作用.
- 阐明Makorin1-p1影响信使RNA稳定性的机制.
- 确定伪基调控对生物体表型的影响,特别是多囊和骨变形.
主要方法:
- 使用了一个转基因插入的突变小鼠模型,具有多囊和骨变形.
- 分析了马科林1-p1伪基因附近的转基因整合对其转录的影响.
- 使用RNA衰变元素分析研究了改变Makorin1-p1转录对Makorin1mRNA稳定性的影响.
- 评估了Makorin1和Makorin1-p1转基因在观察到的表型上的救援潜力.
主要成果:
- 在Makorin1-p1附近插入转基因减少了其转录,导致Makorin1mRNA不稳定.
- 在Makorin1的5'区域内,一种与Makorin1-p1同源的cis作用RNA衰变元素调解了这种效应.
- 马科林1和马科林1-p1转基因都能够拯救多囊和骨变形表型.
- 在控制基因表达方面证明了表达的伪基因的特定调节作用.
结论:
- 表达的伪基因可以发挥积极的调节作用,例如控制信使RNA的稳定性.
- 马科林1-p1通过cis作用的RNA衰变元素影响马科林1mRNA的稳定性,突出显示伪基因介导的基因调节.
- 这些发现强调了非编码RNA和伪基因在生物过程中的功能意义.
- 伪基因代表了一种新的基因调节层,对疾病有潜在的影响.
相关概念视频
01:42What is Gene Expression?
Overview
Gene expression is the process in which DNA directs the synthesis of functional products, that is, proteins. Cells can regulate gene expression at various stages. It allows organisms to generate different cell types and enables cells to adapt to internal and external factors.
Genetic Information Flows from DNA to RNA to Protein
A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is made up of nucleotides and proteins consist of amino...
Gene expression is the process in which DNA directs the synthesis of functional products, that is, proteins. Cells can regulate gene expression at various stages. It allows organisms to generate different cell types and enables cells to adapt to internal and external factors.
Genetic Information Flows from DNA to RNA to Protein
A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is made up of nucleotides and proteins consist of amino...
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,...
02:24Regulation 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...
01:36What is Gene Expression?
A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is comprised of nucleotides and proteins are comprised of amino acids, a mediator is required to convert the information encoded in DNA into proteins. This mediator is the messenger RNA (mRNA). mRNA copies the blueprint from DNA by a process called transcription. In eukaryotes, transcription occurs in the nucleus by complementary base-pairing with the DNA template. The mRNA is then processed and...
02:24Regulation 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...
01:23Regulation 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...