氨酸tRNAs竞争调节氨酸敏感子的mRNA翻译
Veronica Costiniti1,2, Wyatt C Tran1,2, Nandhini Rajesh Babu1,2
1Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA.
Science advances
|November 14, 2025
概括
氨基酸的可用性调节了mRNA翻译效率 (mTE). 血清限制通过ELAC2和tRNA水平,微调蛋白质合成和人类蛋白质组影响mTE.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 生物化学 生物化学
背景情况:
- 不同的mRNA翻译效率 (mTE) 对蛋白质合成和细胞调节至关重要.
- 氨基酸的可用性影响mTE,但其在哺乳动物细胞中的作用尚未完全理解.
- 转移RNA (tRNA) 异受体与mTE编码子有正规联系.
研究的目的:
- 研究哺乳动物细胞中氨基酸对codon mTE的调节.
- 探索ELAC2 (3'tRNA成熟内核酶) 在氨酸 (Ser) 密码子mTE中的作用.
- 解读Ser敏感密码子对mRNA翻译和人类蛋白质组的影响.
主要方法:
- 研究了ELAC2在SER限制下调节Ser编码子mTE中的作用.
- 分析了ELAC2-缺乏细胞中tRNASer异受体水平的变化.
- 解读了Ser敏感密码子对mRNA翻译和全蛋白质组表达的影响.
主要成果:
- ELAC2缺陷恢复了UC[C/U] 血密码子mTE,但在Ser限制下降了AG[U/C] 血密码子mTE.
- 在ELAC2缺乏的细胞中,tRNASer(GCU)水平显著下降.
- 恢复tRNASer(GCU)在ELAC2缺乏细胞中使AG[U/C]mTE正常化,并减少UC[C/U]mTE.
结论:
- 通过ELAC2和tRNASer(GCU)水平介导的血清限制,微调了特定Ser编码子的mTE.
- 调节tRNASer(GCU)影响mRNA翻译并塑造人类蛋白质组.
- 这项研究揭示了哺乳动物细胞中氨基酸依赖的翻译控制的新机制.
更多相关视频
10:18A Fast and Reliable Pipeline for Bacterial Transcriptome Analysis Case study: Serine-dependent Gene Regulation in Streptococcus pneumoniae
Published on: April 25, 2015
10.7K
09:13In vivo Interrogation of Central Nervous System Translatome by Polyribosome Fractionation
Published on: April 30, 2014
12.7K
相关概念视频
Leaky Scanning
5.6K
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...
5.6K
Improving Translational Accuracy
14.0K
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...
14.0K
Translational Regulation
514
Translational regulation in prokaryotes ensures efficient protein synthesis by controlling ribosome access to mRNA. This regulation is mediated by secondary RNA structures, including translational riboswitches, RNA thermometers, and small RNAs (sRNAs), which respond to intracellular and environmental signals to modulate gene expression.Translational RiboswitchesRiboswitches in the leader region of mRNAs can regulate translation by altering the accessibility of the Shine-Dalgarno (SD) sequence,...
514
Initiation of Translation
38.3K
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...
38.3K
Initiation of Translation
7.8K
7.8K
Termination of Translation
27.4K
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...
27.4K
