相关实验视频
Updated: Sep 18, 2025
08:53
A Reporter Based Cellular Assay for Monitoring Splicing Efficiency
Published on: September 15, 2021
2.9K
核糖体RNA转录通过核糖体蛋白RPL2222调节剪接
Wenjun Fan1, Hester Liu1, Gregory C Stachelek1
1Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Cell chemical biology
|June 24, 2025
概括
核糖体的产生是癌症的目标. 新的药物揭示了RPL22突变通过改变RNA剪接来驱动敏感性,揭示了一种新的瘤抑制途径.
科学领域:
- 分子生物学分子生物学
- 癌症生物学 癌症生物学
- 遗传学 遗传学 是一个
背景情况:
- 核糖体生物合成是癌症的一个关键漏洞,通过抑制RNA聚合酶I (Pol I) 转录来向.
- 了解 Pol I 抑制剂的敏感性机制对于开发有效的癌症疗法至关重要.
研究的目的:
- 为了确定 Pol I 抑制剂的敏感性驱动因素.
- 阐明核糖体合成和mRNA拼接之间的机械联系.
- 为了发现由Pol I抑制激活的新型瘤抑制途径.
主要方法:
- 整合来自大型癌细胞小组的多组和药物反应数据.
- 开发和应用特定的Pol I抑制剂.
- 蛋白质-RNA相互作用和mRNA拼接的分析.
- 对rRNA合成的遗传和化学抑制.
主要成果:
- 确定了RPL22框架转移突变为赋予对Pol I抑制剂的敏感性.
- 发现RPL22与28SrRNA和mRNA拼接接口直接相互作用,作为拼接调节器起作用.
- 由于28S rRNA 连接而加剧的 RPL22 缺陷,促进了 RPL22L1 和 MDM4 的拼接.
- 抑制rRNA合成大致重塑mRNA拼接,影响数百个目标.
- 由Pol I抑制逆转RPL22依赖的替代拼接,揭示了一个新的瘤抑制途径.
结论:
- 已经发现了一个强大的机制,将rRNA合成与mRNA剪接联系起来,由RPL22协调.
- 抑制Pol I激活了一个非正规的核糖毒性应激通路,具有抑制瘤的功能.
- RPL22突变代表了在癌症治疗中对Pol I抑制剂敏感性的潜在生物标志物.
相关概念视频
01:23Transcriptional Regulation: Riboswitches
126
Riboswitches are RNA elements that regulate gene expression by altering their secondary structures in response to specific effector molecules. These elements, located in the leader regions of certain mRNAs, act as transcriptional regulators by toggling between alternative conformations to control downstream gene expression. Riboswitch-mediated regulation is a precise mechanism for modulating biosynthetic pathways, as exemplified by the riboflavin biosynthesis pathway in Bacillus...
126
02:53Ribosomal RNA Synthesis
13.5K
Ribosome synthesis is a highly complex and coordinated process involving more than 200 assembly factors. The synthesis and processing of ribosomal components occurs not only in the nucleolus but also in the nucleoplasm and the cytoplasm of eukaryotic cells.
Ribosome biogenesis begins with the synthesis of 5S and 45S pre-rRNAs by distinct RNA polymerases. The primary transcripts are extensively processed and modified before they are bound and folded by ribosomal proteins and assembly factors,...
Ribosome biogenesis begins with the synthesis of 5S and 45S pre-rRNAs by distinct RNA polymerases. The primary transcripts are extensively processed and modified before they are bound and folded by ribosomal proteins and assembly factors,...
13.5K
01:32RNA Splicing
57.2K
Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
57.2K
01:56Riboswitches
8.7K
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...
8.7K
01:23Regulation of Expression at Multiple Steps
1.0K
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...
1.0K
01:29Translational Regulation
110
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,...
110