由氨酸tRNA衍生碎片的翻译抑制的结构基础
Yun Wu1, Meng-Ting Ni1, Ying-Hui Wang1
1Life Sciences Institute, Zhejiang University, Hangzhou, China.
Life science alliance
|April 10, 2024
概括
一个氨酸tRNA片段 (Val-tRF) 结合了古生物学上的核糖体,抑制了蛋白质合成. 冷-EM结构显示,Val-tRF与保存位置结合,阻断翻译并防止核糖体组装.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 生物化学 生物化学
背景情况:
- 非编码RNAs通过微调翻译来调节基因表达.
- tRNA衍生碎片 (tRFs) 是细胞过程的新兴调节者.
- 之前已经证明Val-tRF可以抑制Haloferax volcanii*的翻译.
研究的目的:
- 阐明Val-tRF与古人类核糖体结合的结构基础.
- 了解Val-tRF.RF对翻译抑制的机制.
主要方法:
- 低温电子显微镜 (cryo-EM) 用于确定高分辨率结构.
- 对Val-tRF与*Sulfolobus acidocaldarius*小核糖体子单元结合的结构分析.
主要成果:
- 三个冷EM结构揭示了Val-tRF与保存的核糖体部位结合,包括解码中心.
- tRF结合破坏了关键rRNA螺旋和抗Shine-Dalgarno序列的稳定.
- 瓦尔-tRF结合阻塞了mRNA的P位码子,并以固态方式阻碍了23SrRNA,阻止了70S核糖体的组装.
结论:
- 通过Val-tRF与archaeal核糖体的结合,通过多种机制抑制翻译.
- 结构洞察力解释了tRNA片段如何破坏核糖体功能和组装.
- 这项研究提供了对Val-tRF介导的转化控制的机制性理解.
相关概念视频
Initiation of Translation
32.7K
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...
32.7K
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
Translation
14.8K
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
Proteins are...
Translation Produces the Building Blocks of Life
Proteins are...
14.8K
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
Improving Translational Accuracy
10.3K
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...
10.3K
Transfer RNA Synthesis
11.9K
One of the unique features of tRNA is the presence of modified bases. In some tRNAs, modified bases account for nearly 20% of the total bases in the molecule. Altogether, these unusual bases protect the tRNA from enzymatic degradation by RNases.
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
11.9K


