一个RNA修改阻止了扩展的codon-anticodon相互作用促进+1框架转移
Evelyn M Kimbrough1, Ha An Nguyen1, Haixing Li2,3
1Department of Chemistry, Emory University, Atlanta, GA, USA.
Nature communications
|August 11, 2025
概括
转移RNA (tRNA) 上的N1-甲基瓜诺辛 (m1G) 修改使其在核糖体上的结构稳定. 这种修改可以防止翻译错误,如+1移.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 遗传学 是一个遗传学.
背景情况:
- RNA转录后的修改对于RNA的稳定性和功能至关重要.
- 虽然对信使RNA (mRNA) 的修改得到了充分研究,但它们对转移RNA (tRNA) 稳定性和蛋白质合成精度的影响,特别是在抗外,仍然不太了解.
- 在tRNA修改中的缺陷可能导致翻译错误,包括mRNA框架转移.
研究的目的:
- 调查埃舍里希亚大肠杆菌tRNAProL在第37位的N1-甲基瓜诺辛 (m1G) 修改在防止+1框架转移中的作用.
- 阐明m1G37影响tRNA构造和核糖体功能的结构机制.
主要方法:
- 单分子光共振能量转移 (smFRET) 和冷电子显微镜 (cryo-EM) 的整合.
- 含有野生类型和m1G37缺陷的大肠杆菌的核糖体复合体的结构分析 tRNAProL.
主要成果:
- m1G37的修改是必要的,并且足以调节tRNAProL在核糖体上的构造能量,从而抑制+1框架转移.
- 结构显示,缺乏m1G37的tRNAProL可以在子-子相互作用中形成四个甚至五个基对.
- 这些发现提供了直接的可视化支持的假设,即四个对相互作用可以发生在+1移.
结论:
- 在tRNAProL上的m1G37修改通过防止+1框架转移来维持翻译忠实性,起着至关重要的作用.
- 对m1G37缺乏的tRNAProL-核糖体复合体的结构洞察力为移错误提供了直接的机制解释.
相关概念视频
Mutations
84.2K
Overview
84.2K
Nonsense-mediated mRNA Decay
10.8K
The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
10.8K
RNA Editing
9.2K
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...
9.2K
Point and Frameshift Mutations
86
Point mutations are genetic alterations involving the change of a single nucleotide base pair in DNA. Depending on how the alteration affects protein synthesis, they can lead to various consequences.Point mutations fall into the following types:Silent mutations occur when a nucleotide change does not alter the amino acid sequence due to the redundancy of the genetic code. For instance, changing ACC to ACA still encodes threonine, leaving the protein function unaffected. This occurs because...
86
Transfer RNA Synthesis
12.2K
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...
12.2K
Nuclear Export of mRNA
7.9K
Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
7.9K


