40S核糖体蛋白,RPS26和RPS25的不足会在脆弱X相关条件下对含有多糖素的蛋白质的生物合成产生负面影响
Katarzyna Tutak1, Izabela Broniarek1, Andrzej Zielezinski2
1Department of Gene Expression, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University, Uniwersytetu Poznańskiego 6, Poznan, Poland.
eLife
|May 16, 2025
概括
研究人员确定了核糖体蛋白RPS26和RPS25以及伴侣TSR2,作为FMR1基因的重复关联非AUG启动 (RAN) 翻译中的关键参与者. 调节这些因素会影响脆弱的X相关疾病中有毒的FMRpolyG蛋白质的产生.
科学领域:
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
- 神经科学是一个神经科学.
背景情况:
- 在FMR1基因中CGG重复扩张导致脆弱的X前变异疾病.
- 一个常见的机制是重复关联的非AUG启动 (RAN) 翻译,产生有毒的FMRpolyG蛋白.
- 识别RAN翻译的修饰剂对于理解这些疾病至关重要.
研究的目的:
- 为了确定CGG重复关联RAN转换的新型修饰剂.
- 调查已识别的修饰剂在FMRpolyG产生和毒性的作用.
主要方法:
- 使用RNA标记系统和质谱仪进行查.
- 采用纤维素实验来评估CGGexp含有FMR1RNA的蛋白质丰富性.
- 进行了基因消耗和沉默实验 (RPS26,TSR2,RPS25).
主要成果:
- 鉴定了由CGGexp-FMR1RNA丰富的核糖体蛋白RPS26和伴侣TSR2.
- 耗尽RPS26或TSR2调制的FMRpolyG的产生和毒性.
- RPS26 缺陷影响了特定蛋白质的转化,具有短,富含 GC 的 5'UTR.
- 抑制RPS25也抑制了FMRpolyG生物合成.
结论:
- 在CGG重复关联RAN转换中,RPS26,TSR2和RPS25发挥着重要的作用.
- 这些发现凸显了40S核糖体蛋白在非正规翻译中的参与.
- 对于脆弱的X前变异疾病的潜在治疗标可能涉及调节这些因素.
相关概念视频
Translation
14.2K
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...
14.2K
Amyloid Fibrils
9.1K
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
9.1K
Ribosomal RNA Synthesis
13.0K
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,...
13.0K
Ribosome Profiling
3.4K
Ribosome profiling or ribo-sequencing is a deep sequencing technique that produces a snapshot of active translation in a cell. It selectively sequences the mRNAs protected by ribosomes to get an insight into a cell’s translation landscape at any given point in time.
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique...
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique...
3.4K
RNA Splicing
55.8K
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...
55.8K
Riboswitches
8.0K
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...
8.0K


