通过由腺病毒核心蛋白VII引发的NPM1-介导相分离来进行核重组
Michelle Jane Genoveso1, Mitsuru Okuwaki2, Kohsuke Kato1
1Department of Infection Biology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
Microbiology spectrum
|August 20, 2024
概括
腺病毒劫持宿主细胞液体-液体相分离 (LLPS) 使用核蛋白NPM1包装病毒DNA. 抑制NPM1介导的LLPS通过损害基因组包装来破坏病毒复制.
科学领域:
- 细胞生物学 细胞生物学
- 病毒学 病毒学
- 生物化学 生物化学
背景情况:
- 液-液相分离 (LLPS) 驱动着无膜核区的形成.
- 病毒感染通过LLPS诱导显著的核重组,影响病毒复制.
- 确切的机制和LLPS在病毒复制中的作用尚未完全理解.
研究的目的:
- 研究核蛋白NPM1介导LLPS在腺病毒复制中的作用.
- 阐明NPM1如何与腺病毒蛋白VII相互作用,形成病毒诱导的复制后体 (ViPR).
- 确定NPM1介导的LLPS对病毒基因组包装的影响.
主要方法:
- 研究了NPM1在对腺病毒感染的反应中对LLPS的活性.
- 利用1,6-hexanediol来抑制LLPS和观察到的蛋白VII局部化.
- 进行了光漂白实验,以评估ViPR体中的EGFP-NPM1的动态.
- 耗尽了NPM1以评估其对病毒基因组包装的影响.
主要成果:
- NPM1的LLPS活性对于腺病毒蛋白VII沉积到ViPR体内至关重要.
- NPM1与蛋白VII相互作用,启动LLPS并形成ViPR体.
- 抑制LLPS导致了蛋白VII的分散,而NPM1的枯竭减少了病毒基因组的包装.
- 在ViPR体内,NPM1表现出类似流体的特性.
结论:
- 在ViPR体内的腺病毒蛋白VII积累是由NPM1诱导的LLPS介导的.
- NPM1充当分子陪伴者,通过LLPS促进病毒染色质组合.
- 通过NPM1介导的LLPS是一种关键的宿主病毒相互作用,促进有效的腺病毒复制.
相关概念视频
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
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
Methods of Nuclear Reprogramming
1.8K
Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for...
1.8K
Introduction to Nuclear Reprogramming
1.9K
Nuclear reprogramming is the process of switching gene expression of one cell type to that of another cell type, usually from a differentiated cell state to an undifferentiated cell state. Differentiation occurs during processes such as development and morphogenesis, tissue regeneration, and malignancy. Cells can also be artificially induced to reprogram their gene expression by techniques such as nuclear transfer, induced pluripotency, and cell fusion. Such techniques have many applications in...
1.9K
Disassembly of Intermediate Filaments
2.0K
Intermediate filaments (IFs) do not undergo spontaneous disassembly. Enzymes, kinases, and phosphatases add and remove phosphates from specific sites to regulate their disassembly. The IF concentration in the cytoplasm also regulates the disassembly. If the concentration crosses a threshold, it activates the protein kinases in the vicinity, allowing the phosphorylation of IFs.
Keratin proteins, found at the cell periphery near cell junctions, undergo a cycle of assembly and disassembly. In Type...
Keratin proteins, found at the cell periphery near cell junctions, undergo a cycle of assembly and disassembly. In Type...
2.0K
Nuclear Localization Signals and Import
5.6K
Proteins targeted to the nucleus carry short stretches of amino acid sequences called the nuclear localization signal or NLS. Classical nuclear localization signals are of two types: monopartite and bipartite NLS. Monopartite classical NLS (cNLS) consists of a single cluster of 4-8 amino acids. Bipartite cNLS consists of two clusters of 2-3 amino acids and a 9-12 residue long proline-rich linker bridging the two clusters. Signal clusters are rich in positively charged amino acids such as...
5.6K


