一个动态的组成平衡控制了eIF3对mRNA的识别
Nicholas A Ide1, Riley C Gentry1, Margaret A Rudbach2
1Department of Biological Sciences, Columbia University, New York, NY, USA.
bioRxiv : the preprint server for biology
|May 7, 2024
概括
细胞转化启动因子3 (eIF3) 在不同形式之间动态交换. eIF3a子单元,而不是完整的复合体,驱动mRNA结合,揭示了翻译启动的新模式.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生化学
背景情况:
- 细胞转化启动因子3 (eIF3) 是一个关键的多子单元复合体,调节蛋白质合成.
- 对eIF3如何协调其在翻译启动中的多种功能缺乏全面的理解.
- eIF3与核糖体和信使RNA (mRNA) 相互作用,以促进翻译.
研究的目的:
- 阐明eIF3复合体的动态性质和组成平衡.
- 为了确定负责mRNA结合的特定eIF3亚种.
- 为eIF3在翻译启动中的作用建立一个机制框架.
主要方法:
- 用单分子光散射显微镜研究酵母中的eIF3动态.
- 为了进一步研究,使用了体外复制的eIF3系统.
- 进行了生化分析,以补充显微镜发现.
主要成果:
- 糖菌 (Saccharomyces cerevisiae) eIF3存在于其全复合体,子复合体和单个子单元之间的动态交换中.
- 在特定的eIF3a含有子复合体内,mRNA结合是由eIF3a子单元介导的,而不是整个eIF3复合体.
- 该研究确定了参与eIF3.3动态组成平衡的亚种.
结论:
- 这些发现为eIF3在翻译过程中的mRNA招募中的功能提供了一个机制模型.
- 这项工作为研究eIF3.3的多方面的活动建立了基础框架.
- 了解eIF3的动态是理解翻译法规的关键.
相关概念视频
Nonsense-mediated mRNA Decay
10.6K
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,...
10.6K
Initiation of Translation
32.6K
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...
32.6K
mRNA Stability and Gene Expression
5.6K
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
5.6K
Nuclear Export of mRNA
7.7K
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...
7.7K
Regulated mRNA Transport
6.3K
In eukaryotes, transcription and translation are compartmentalized; an mRNA is first synthesized in the nucleus and then selectively transported to the cytoplasm for protein synthesis. Before transport, a pre-mRNA undergoes several steps of post-transcriptional modifications including splicing, 5' capping, and the addition of a poly-adenine tail. Various proteins bind to the pre-mRNA during these modifications. The mRNA transport takes place with the help of multiple proteins playing...
6.3K
Regulation of Expression Occurs at Multiple Steps
22.6K
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...
22.6K


