从旁边:组织特异性核蛋白在健康和疾病中的功能,一个更新
Ramona Jühlen1, Birthe Fahrenkrog2
1Institute of Biochemistry and Molecular Cell Biology, Medical School, RWTH Aachen University, Aachen, Germany.
FEBS letters
|October 24, 2023
概括
核蛋白的突变,形成核毛孔综合体的蛋白质,导致罕见的遗传性疾病,影响心脏,脏和大脑等器官. 研究正在揭示疾病机制.
科学领域:
- 细胞生物学 细胞生物学
- 遗传学 遗传学 是一个
- 人类疾病 人类疾病
背景情况:
- 细胞需要选择性核细胞质运输来起作用,由核孔综合体 (NPC) 调节.
- NPC是由核波林组成的;异常表达与癌症和自身免疫性疾病有关.
- 下一代测序已经确定了核蛋白基因的突变,导致罕见的遗传性疾病.
研究的目的:
- 审查最近关于人类遗传性疾病中改变核蛋白功能的研究结果.
- 突出新兴的机制性见解与核酸相关的疾病.
主要方法:
- 关于核波林和遗传性疾病研究的文献综述.
- 对确定核基因突变的下一代测序数据的分析.
- 综合目前对与核蛋白变化相关的疾病机制的理解.
主要成果:
- 脚手架核蛋白的突变主要影响内部器官 (心脏,脏,卵巢).
- 外围核氨酸的遗传变化主要影响中枢神经系统和发育.
- 鉴定出的突变和相关疾病的数量正在迅速增加.
结论:
- 核蛋白突变是各种人类遗传疾病的日益严重的原因.
- 了解核蛋白的功能对于诊断和治疗这些疾病至关重要.
- 对疾病机制的进一步研究对于治疗开发至关重要.
相关概念视频
The Nucleolus
8.9K
The nucleolus is the most prominent substructure of the nucleus. When it was first discovered, it was considered to be an isolated organelle that forms fibrils and granules. In 1931, the relationship between the nucleolus and chromosomes was first described by Heitz. He observed that the appearance and size of nucleolus varies depending on the stage of the cell cycle. He also noticed constricted regions on different chromosomes clustered together at definite cell cycle stages. These regions,...
8.9K
Regulation of Nuclear Protein Sorting
2.4K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
Nuclear Protein Sorting
4.6K
Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
4.6K
Nucleosome Remodeling
9.2K
Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
9.2K
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
Directionality of Nuclear Transport
3.3K
Ras-related nuclear protein or Ran is a small G protein that cycles between its GTP and GDP bound states. Ran specific regulators, a Ran GTPase Activating Protein or RanGAP present in the cytosol and a Ran guanine nucleotide exchange factor or RanGEF present inside the nucleus regulate GTP/GDP exchange. A high concentration of GTP inside the cells, in addition to this asymmetric distribution of Ran-specific regulators, leads to a higher RanGTP concentration inside the nucleus. This...
3.3K


