从RNA的尾端解码ALS
Yusuke Fujioka1, Shinsuke Ishigaki1
1Molecular Neuroscience Research Center, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan.
Cell genomics
|December 11, 2025
概括
研究人员创建了一个单核的ALS/FTLD脑组织的转录图集. 他们发现了替代多基解的广泛变化,将RNA处理与疾病机制联系起来.
科学领域:
- 神经科学是一个神经科学.
- 基因组学就是基因组学.
- 分子生物学分子生物学
背景情况:
- 肌缩侧面硬化症 (ALS) 和前叶退行症 (FTLD) 是具有复杂遗传和分子基础的衰弱性神经退行性疾病.
- 了解驱动ALS/FTLD神经元功能障碍和死亡的分子机制对于开发有效疗法至关重要.
研究的目的:
- 创建一个全面的单核转录基因地图人脑受ALS/FTLD影响.
- 研究替代多基化 (APA) 在ALS/FTLD分子病理学中的作用.
主要方法:
- 单核RNA测序 (snRNA-seq) 在ALS/FTLD患者和对照患者的死后脑组织上进行.
- 生物信息分析被用来识别不同细胞类型的差异表达基因和APA事件.
主要成果:
- 建立了ALS/FTLD大脑的详细的转录图谱图谱,揭示了细胞类型特定的基因表达模式.
- 在ALS/FTLD中,在神经元和其他大脑细胞中观察到替代多基解的广泛变化.
- 发现APA变化与应激反应和神经退行相关的途径有关.
结论:
- 替代多基化是一种重要的分子机制,在ALS/FTLD中失调.
- 3'端RNA处理作为细胞应激,细胞类型认同和大脑疾病易感性的关键整合剂.
- 这些发现为ALS/FTLD病原体提供了新的机制性见解,并建议与RNA处理相关的潜在治疗点.
更多相关视频
08:59Real-Time Fluorescent Measurement of Synaptic Functions in Models of Amyotrophic Lateral Sclerosis
Published on: July 16, 2021
3.0K
11:46Production of RNA for Transcriptomic Analysis from Mouse Spinal Cord Motor Neuron Cell Bodies by Laser Capture Microdissection
Published on: January 13, 2014
11.1K
相关概念视频
Leaky Scanning
5.6K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.6K
Nonsense-mediated mRNA Decay
11.6K
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,...
11.6K
Nonsense-mediated mRNA Decay
3.2K
3.2K
Ribosome Profiling
4.0K
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...
4.0K
RNA Splicing
60.2K
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...
60.2K
pre-mRNA Processing
57.0K
In eukaryotic cells, transcripts made by RNA polymerase are modified and processed before exiting the nucleus. Unprocessed RNA is called precursor mRNA or pre-mRNA to distinguish it from mature mRNA.
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a “cap” to the 5’ end of the growing transcript. In this process, a 5’ phosphate is replaced by modified guanosine that has a methyl group attached to it (7-Methyl...
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a “cap” to the 5’ end of the growing transcript. In this process, a 5’ phosphate is replaced by modified guanosine that has a methyl group attached to it (7-Methyl...
57.0K
