细胞NS1-BP蛋白与mRNA输出受体NXF1相互作用,以调解流感病毒M mRNAs的核输出
Ke Zhang1, Tolga Cagatay2, Dongqi Xie2
1Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas, USA; Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai, China.
The Journal of biological chemistry
|October 9, 2024
概括
流感病毒NS1蛋白通常会阻断mRNA的输出. 然而,NS1结合蛋白 (NS1-BP) 通过竞争出口因素来促进M1和M2mRNA的出口,从而使病毒复制.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 流感A病毒利用宿主细胞机械进行复制,包括核转录和mRNA处理.
- 病毒非结构蛋白1 (NS1) 干扰宿主mRNA输出,而NS1结合蛋白 (NS1-BP) 促进M1到M2的拼接.
- NS1与mRNA输出受体核RNA输出因子-1 (NXF1) 结合,抑制细胞mRNA的输出.
研究的目的:
- 为了阐明M1和M2mRNA从核中输出,尽管NS1介导的抑制的机制.
- 调查NS1-BP在病毒M1和M2mRNA核出口中的作用.
主要方法:
- 生物化学测试用于研究蛋白质-蛋白质和蛋白质-RNA相互作用.
- 细胞生物学技术可视化和跟踪感染细胞内的mRNA和蛋白质定位.
- 在关键相互作用蛋白质的存在和缺席下对病毒复制的分析.
主要成果:
- NS1-BP与NS1竞争与NXF1结合,使NXF1能够被M mRNA招募.
- NS1-BP,NS1,NXF1和生殖中心关联核蛋白的复合物有助于M mRNA的输出.
- 病毒蛋白的解离发生在核孔综合体,允许M mRNA转移到细胞质.
结论:
- 描述了病毒mRNA核出口的新途径,克服了NS1介导的抑制.
- NS1-BP作为关键的病毒宿主因子,调解病毒复制的M mRNA输出.
- 了解这些病毒与宿主相互作用对于开发抗流感抗病毒策略至关重要.
相关概念视频
Nuclear Export
3.6K
The nucleus restricts several proteins within and allows others to pass. The restricted proteins possess a nuclear retention sequence or NRS, anchoring them to the nuclear lamins and preventing their transport to the cytosol. The non-restricted proteins, after their synthesis, are transported to their site of action, such as the cytosol or other organelles, with the help of nuclear export signals or NES.
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
3.6K
Nuclear Export of mRNA
7.6K
Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
7.6K
Leaky Scanning
5.1K
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...
5.1K
Regulated mRNA Transport
6.3K
In eukaryotes, transcription and translation are compartmentalized; an mRNA is first synthesized in the nucleus and then selectively transported to the cytoplasm for protein synthesis. Before transport, a pre-mRNA undergoes several steps of post-transcriptional modifications including splicing, 5' capping, and the addition of a poly-adenine tail. Various proteins bind to the pre-mRNA during these modifications. The mRNA transport takes place with the help of multiple proteins playing...
6.3K
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


