烯胺激素会触发酵母酵母中低基改性tRNA的衰变
Katharina Görlitz1, Larissa Bessler2, Mark Helm2
1Institute of Biology, Department of Microbiology, Universität Kassel, Kassel 34132, Germany.
Nucleic acids research
|May 8, 2024
概括
抑制tRNA甲基化可以通过促进转移RNA (tRNA) 的降解来增强5-甲 (5-FU) 和5-细胞素 (5-FC) 的细胞毒性. 这一发现表明了改善癌症和真菌感染治疗的策略.
科学领域:
- 分子生物学分子生物学
- 菌类学 菌类学是指菌类学.
- 药理学 药理学 是一个学科.
背景情况:
- 治疗性胺素,5-甲 (5-FU) 和5-细胞素 (5-FC),在治疗癌症和真菌感染方面至关重要.
- 这些药物形成5 - 氨酸三酸盐,它集成到细胞RNA中.
研究的目的:
- 使用Saccharomyces cerevisiae研究tRNA甲基化在氧胺诱导的细胞毒性中的作用.
- 阐明低甲基化tRNA对药物毒性的作用机制.
主要方法:
- 使用了模型真菌Saccharomyces cerevisiae.
- 使用遗传方法研究tRNA甲基转移酶淘汰 (Trm4,Trm8).
- 量化了tRNA修饰水平和评估了涉及Xrn1.1.的tRNA降解途径.
主要成果:
- 甲胺显著增强了缺乏Trm4和Trm8依赖甲基化的tRNAValAAC的降解.
- 这种增强的降解在高温下加剧,即使仅仅是Trm8缺乏.
- 药物诱导的尿素修饰损失和Xrn1激活tRNAValAAC衰变有助于细胞毒性增加.
结论:
- 缺少特定的tRNA甲基化可能会增强 pyrimidine 的细胞毒性.
- 抑制tRNA甲基化的策略可以提高5-FU和5-FC的治疗疗效.
- 向tRNA修饰途径可能为抗真菌和抗癌疗法提供新的途径.
更多相关视频
相关概念视频
Nuclear Export of mRNA
7.7K
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...
7.7K
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
Riboswitches
8.1K
Riboswitches are non-coding mRNA domains that regulate the transcription and translation of downstream genes without the help of proteins. Riboswitches bind directly to a metabolite and can form unique stem-loop or hairpin structures in response to the amount of the metabolite present. They have two distinct regions – a metabolite-binding aptamer and an expression platform.
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
8.1K
Transcription Attenuation in Prokaryotes
15.3K
Transcriptional attenuation occurs when RNA transcription is prematurely terminated due to the formation of a terminator mRNA hairpin structure. Bacteria use these hairpins to regulate the transcription process and control the synthesis of several amino acids including histidine, lysine, threonine, and phenylalanine. Transcription attenuation takes place in the non-coding regions of mRNA.
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
15.3K
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
mRNA Stability and Gene Expression
5.6K
The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
Cis-acting Elements involved in mRNA stability
Cis-acting Elements involved in mRNA stability
5.6K


