原生CFTR编码子偏差控制转化速率,以平衡非路径聚合和道功能,通过构造性印记
Jae Seok Yoon1, Hongyu Li2, Yonjung Kim3
1CFFT Lab, Cystic Fibrosis Foundation, 44 Hartwell Ave., Lexington, MA, 02421, USA. jyoon@cff.org.
Scientific reports
|December 12, 2025
概括
囊性纤维化转膜导电调节器 (CFTR) 中的同名编码子影响蛋白质折叠和功能. 修改编码子使用改变了CFTR聚合,并增强了其化物通道活性.
科学领域:
- 分子生物学分子生物学
- 生物物理学的生物物理.
- 遗传学 是一个遗传学.
背景情况:
- 活体中蛋白质折叠受到包括同义代码子使用在内的因素的调节,这影响了转化速率.
- 囊性纤维化跨膜导电调节器 (CFTR) 对于离子运输至关重要,其正确的折叠和功能至关重要.
研究的目的:
- 调查CFTR第一个核酸结合域 (NBD1) 中本源子使用对其合成,折叠和功能的作用.
- 确定改变同名编码子使用对CFTR处理,聚合和通道活动的影响.
主要方法:
- 分析CFTR NBD1序列中原生和修饰同名编码子的使用情况.
- 使用细胞测试评估CFTR蛋白折叠,聚合和处理.
- 测量CFTR化通道功能,包括依赖ATP的门.
主要成果:
- 在NBD1中使用本机CFTR码子会诱导一种影响折叠和处理的翻译暂停.
- 通过同义代码子替代消除这种暂停,增加了不成熟的CFTR聚合.
- 成熟的CFTR具有改变的编码子使用表现出增强的ATP依赖的化物通道门.
结论:
- 在CFTR合成过程中同义子的使用印记了持久的结构和功能性质.
- CFTR编码子的使用代表了防止蛋白质聚合和优化通道功能之间的进化平衡.
相关概念视频
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
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
Translation
17.4K
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...
17.4K
Translation
154.9K
Lesson: Translation
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...
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...
154.9K
Genome Copying Errors
5.0K
DNA replication is a well-evolved process that copies millions of base pairs with high fidelity during each cell division. Occasionally a wrong base or a long stretch of wrong bases may get added to the daughter strands. If the errors are left unchecked, cells might accumulate several mutations that might endanger their survival. Therefore, the copying errors are checked and repaired at three levels.
5.0K
RNA Editing
9.7K
RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...
9.7K


