在真核生物中停止子识别的结构基础
Alan Brown1, Sichen Shao1, Jason Murray1
1MRC-LMB, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
Nature
|August 7, 2015
概括
细胞释放因子1 (eRF1) 识别了所有三个停止密码. 新的冷电子显微镜结构揭示了ERF1如何使用核糖体RNA压缩信使RNA,从而实现精确的停止密码区分.
科学领域:
- 分子生物学
- 结构生物学
- 遗传学
背景情况:
- 蛋白质合成终结依赖于在核糖体的A位点中识别停止子 (UAA,UAG,UGA).
- 细菌使用不同的释放因子,而真核生物使用单一的全能释放因子 (eRF1).
- 通过 eRF1 区分停止编码子和感应编码子的机制尚不清楚.
研究的目的:
- 通过 eRF1 阐明真核停止子识别的分子基础.
- 确定 eRF1,核糖体和停止之间的结构相互作用.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来获得高分辨率结构 (3.5-3.8 Å).
- 分析了与eRF1结合的哺乳动物核糖体复合体和三个停止.
主要成果:
- eRF1结合诱导了18S核糖体RNA的结构变化,转换了核酸A1825.
- 这种核酸堆叠在第二个和第三个停止基上,压缩信使RNA.
- 在rRNA和eRF1残留物之间的结网进一步稳定了停止子的识别.
结论:
- 这项研究为 eRF1 如何实现真核停止特异性提供了分子框架.
- eRF1利用核糖体RNA核酸,也参与tRNA选择,以促进信使RNA的紧缩.
- 这些发现提供了关于正规和过早翻译终止机制的见解.
相关概念视频
Leaky Scanning
5.9K
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...
5.9K
From DNA to Protein
24.6K
The flow of genetic information in cells from DNA to mRNA to protein is described by the central dogma, which states that genes specify the sequence of mRNAs, which in turn specify the sequence of amino acids making up all proteins. The decoding of one molecule to another is performed by specific proteins and RNAs. Because the information stored in DNA is so central to cellular function, it makes intuitive sense that the cell would make mRNA copies of this information for protein synthesis...
24.6K
Nonsense-mediated mRNA Decay
12.2K
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,...
12.2K
Nonsense-mediated mRNA Decay
3.7K
3.7K
Initiation of Translation
40.4K
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...
40.4K
Prokaryotic Gene Structure and Organization
2.9K
Prokaryotic genomes exhibit a streamlined organization of coding and non-coding regions essential for gene expression and protein synthesis. While coding regions contain the genetic instructions for proteins or functional RNAs, non-coding regions regulate the precise transcription and translation of these genes.Coding Regions: Proteins and RNAsThe primary coding regions, known as structural genes, include sequences transcribed into messenger RNA (mRNA) and ultimately translated into...
2.9K


