自调节mRNA基因电路的设计
1Department of Mathematics, University of York, York, YO10 5DD, UK. eric.dykeman@york.ac.uk.
Scientific reports
|August 21, 2024
概括
研究人员设计了自我调节的信使RNA (mRNA) 分子,可以控制蛋白质的产生,而不会影响转录. 这一突破使合成生物学和疫苗应用中精确的蛋白质水平控制成为可能.
科学领域:
- 分子生物学分子生物学
- 合成生物学 合成生物学
- 病毒学 病毒学
背景情况:
- 在体内蛋白质表达通常由转录反机制调节.
- 阳性感单链RNA病毒通常通过mRNA二次结构控制蛋白质的表达,例如内部核糖体进入点.
- 这种病毒自我调节表明设计人工自我调节mRNA的潜力.
研究的目的:
- 为了证明设计自我调节的信使RNA (mRNA) 分子的可行性.
- 为控制蛋白质表达创建一个概念验证的多基斯特龙mRNA系统.
- 探索在合成生物学和疫苗开发中需要精确的蛋白质水平控制的应用.
主要方法:
- 设计了一种基于菌体MS2的多基斯特龙mRNA.
- 设计了一个上游基因来抑制下游基因的合成.
- 利用计算工具来模拟核糖体动力学和共同翻译的mRNA折叠.
主要成果:
- 确定了增强翻译效率的特定mRNA突变.
- 证明突变可以改善下游基因表达的抑制.
- 验证了自我调节mRNA控制蛋白质合成的概念.
结论:
- 自调节的mRNA基因电路可以设计用于精确控制细胞蛋白质水平.
- 这种方法为开发基于mRNA的疗法和疫苗提供了一种新的策略.
- 这些发现为合成生物学中定制mRNA工程开辟了可能性.
相关概念视频
Regulation of Expression Occurs at Multiple Steps
22.5K
Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
22.5K
Regulation of Expression at Multiple Steps
875
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
875
What is Gene Expression?
8.5K
A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is comprised of nucleotides and proteins are comprised of amino acids, a mediator is required to convert the information encoded in DNA into proteins. This mediator is the messenger RNA (mRNA). mRNA copies the blueprint from DNA by a process called transcription. In eukaryotes, transcription occurs in the nucleus by complementary base-pairing with the DNA template. The mRNA is then...
8.5K
Regulated mRNA Transport
6.3K
In eukaryotes, transcription and translation are compartmentalized; an mRNA is first synthesized in the nucleus and then selectively transported to the cytoplasm for protein synthesis. Before transport, a pre-mRNA undergoes several steps of post-transcriptional modifications including splicing, 5' capping, and the addition of a poly-adenine tail. Various proteins bind to the pre-mRNA during these modifications. The mRNA transport takes place with the help of multiple proteins playing...
6.3K
Nuclear Export of mRNA
7.6K
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...
7.6K
Nonsense-mediated mRNA Decay
10.6K
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,...
10.6K


