同义代码的使用调节了翻译启动的过程
Chloe L Barrington1, Gabriel Galindo2, Amanda L Koch2
1Department of Biochemistry & Molecular Genetics, University of Colorado School of Medicine, Aurora, CO 80045, USA; RNA Bioscience Initiative, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Cell reports
|December 14, 2023
概括
非最佳的同名编码子通过抑制翻译启动来减少基因表达,而不仅仅是mRNA降解. 这种编码子使用法规通过降低启动率和因子结合来影响蛋白质水平.
科学领域:
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
- 基因表达规则 基因表达规则
背景情况:
- 同义代码子的使用影响基因表达,而非最佳代码子以前与更慢的翻译和mRNA衰变有关.
- 然而,单独的转录水平不能完全解释观察到的蛋白质丰度变化,这表明了额外的调节层.
研究的目的:
- 为了研究子使用影响蛋白质水平超出mRNA降解的机制.
- 为了确定非最佳的编码子是否会影响翻译启动率.
主要方法:
- 利用人类和果虫细胞中的记者系统来量化蛋白质和转录水平.
- 评估了翻译启动因子 (eIF4E,eIF4G1) 与非最佳转录的结合.
主要成果:
- 的使用变化通过转录水平解释了不到一半的蛋白质丰度差异.
- 非最佳的编码子显著抑制翻译启动,独立于mRNA衰变.
- 非最佳的转录表现出对翻译启动因子eIF4E和eIF4G1.1的结合减少.
结论:
- 非最佳的同名编码子通过抑制翻译启动来代表一个强大的调节机制.
- 这种抑制是独立于mRNA衰变和死亡化发生的,不涉及CNOT3.3.
- 通过翻译启动效率,Codon的使用直接调节蛋白质合成速率.
相关概念视频
Initiation of Translation
33.5K
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...
33.5K
Leaky Scanning
5.1K
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...
5.1K
Improving Translational Accuracy
11.0K
Base complementarity between the three base pairs of mRNA codon and the tRNA anticodon is not a failsafe mechanism. Inaccuracies can range from a single mismatch to no correct base pairing at all. The free energy difference between the correct and nearly correct base pairs can be as small as 3 kcal/ mol. With complementarity being the only proofreading step, the estimated error frequency would be one wrong amino acid in every 100 amino acids incorporated. However, error frequencies observed in...
11.0K
From DNA to Protein
18.4K
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...
18.4K
Regulation of Expression at Multiple Steps
916
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...
916
Termination of Translation
25.4K
The large ribosomal subunit has several important structures essential to translation. These include the peptidyl transferase center (PTC) - which is the site where the peptide bond is formed - and a large, internal, water-filled tube through which the nascent polypeptide moves. This latter structure is called the Peptide Exit Tunnel, and it begins at the PTC and spans the body of the large ribosomal subunit. During translation, as the nascent polypeptide chain is synthesized, it passes through...
25.4K


