关键的cis-参数影响结构辅助RNA翻译 (START) 在真核生物中非AUG编码的启动
Antonin Tidu1, Fatima Alghoul1, Laurence Despons1
1Université de Strasbourg, Institut de Biologie Moléculaire et Cellulaire, Architecture et Réactivité de l'ARN, CNRS UPR9002, 2 allée Konrad Roentgen, F-67084 Strasbourg, France.
NAR genomics and bioinformatics
|June 12, 2024
概括
下游RNA结构可以通过阻断扫描核糖体来促进非AUG启动编码子的翻译启动. 这种结构辅助RNA翻译 (START) 机制在人类中很普遍,影响了替代翻译启动.
科学领域:
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
- 生物信息学是一种生物信息学.
背景情况:
- 转化启动在真核生物中是一个复杂的,受调节的过程,涉及 cis 调节序列和转化作用因子,如真核生物启动因子 (eIF).
- 一个关键的步骤是43S预启动复合体扫描,用于启动核糖体组装和蛋白质合成的启动代码.
研究的目的:
- 调查下游二次结构在STructure-Assisted RNA翻译 (START) 机制中对AUG和非AUG启动的作用.
- 确定下游结构的最佳条件,以促进非AUG翻译的启动.
主要方法:
- 对二次结构稳定性和与非AUG编码子相对位置的分析.
- 在Homo sapiens中对替代翻译启动位点进行全基因组分析.
- 使用选定的上游开放阅读框架 (uORFs) 验证下游结构对翻译启动的影响.
主要成果:
- 下游的二次结构可以通过阻断43S粒子和稳定子-抗子配对来促进非AUG翻译启动.
- 这些结构所需的稳定性因不同细胞类型而异.
- 大约25%的人类替代翻译启动站点拥有能够促进START的下游结构,无论启动代码是什么.
结论:
- 下游RNA结构在调节翻译启动方面发挥着重要作用,特别是通过START机制对非AUG启动密码子起到重要作用.
- START机制是人类翻译领域的一个保存和广泛的监管策略.
- 了解START提供了对替代翻译和基因表达调节的见解.
相关概念视频
Initiation of Translation
32.5K
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...
32.5K
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
10.1K
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...
10.1K
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
tRNA Activation
19.2K
Aminoacyl-tRNA synthetases are present in both eukaryotes and bacteria. Though eukaryotes have 20 different aminoacyl-tRNA synthetases to couple to 20 amino acids, many bacteria do not have genes for all of these aminoacyl-tRNA synthetases. Despite this, they still use all 20 amino acids to synthesize their proteins. For instance, some bacteria do not have the gene encoding the enzyme that couples glutamine with its partner tRNA. In these organisms, one enzyme adds glutamic acid to all of the...
19.2K
Chromatin Structure Regulates pre-mRNA Processing
7.0K
In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
The chromatin structure, especially...
7.0K


