通过蛋白调节的上游开放阅读框架进行翻译控制
Jan Medenbach1, Markus Seiler, Matthias W Hentze
1European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Cell
|June 14, 2011
概括
性致命 (SXL) 蛋白通过mRNA的上游开放阅读框架 (uORF) 调节翻译. 在uORFs附近的SXL结合通过控制翻译启动来抑制蛋白质合成.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 发展生物学 发展生物学
背景情况:
- 在Drosophila中,剂量补偿对于性发育至关重要.
- 性致命 (SXL) 蛋白在这个过程中起着关键作用.
- 转化控制机制对于基因表达调节至关重要.
研究的目的:
- 研究SXL调节msl-2mRNA转换的机制.
- 确定涉及翻译控制的共同监管要素.
- 探索这个监管机制的更广泛的适用性.
主要方法:
- 分析mRNA序列和5'未翻译区域 (UTR).
- 研究SXL和RNA结合蛋白之间的相互作用.
- 在上游开放阅读框架 (uORF) 中研究核糖体扫描和翻译启动.
- 在异质系统中的实验验证.
主要成果:
- 短 uORF 下游的 SXL 绑定强烈抑制了主要阅读框架的翻译.
- 这种抑制是通过增加uORF的核糖体启动和阻碍下游翻译来实现的.
- SXL的监管效果专门针对翻译的启动,而不是延长或终止.
- 已识别的调节模块在不同的生物环境中起作用,并且存在于其他Drosophila mRNA中.
结论:
- 蛋白调节的uORFs代表了控制蛋白质合成的系统机制.
- 这种涉及SXL和uORF的转化控制模式是基因调节的一个重要发现.
- 发现的调节模块对理解不同系统的基因表达有影响.
相关概念视频
Translational Regulation
Translational regulation in prokaryotes ensures efficient protein synthesis by controlling ribosome access to mRNA. This regulation is mediated by secondary RNA structures, including translational riboswitches, RNA thermometers, and small RNAs (sRNAs), which respond to intracellular and environmental signals to modulate gene expression.Translational RiboswitchesRiboswitches in the leader region of mRNAs can regulate translation by altering the accessibility of the Shine-Dalgarno (SD) sequence,...
Regulation 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...
Regulation 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...
Regulation 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...
Leaky Scanning
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R stands for...
Initiation of Translation
Initiating translation is complex because it involves multiple molecules. Initiator tRNA, ribosomal subunits, and eukaryotic initiation factors (eIFs) are all required to assemble on the initiation codon of mRNA. This process consists of several steps that are mediated by different eIFs.
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...


