SARS CoV irottaa nukleoporiini NUP93 :n NPC kompleksista

https://pubmed.ncbi.nlm.nih.gov/30943371/

 2019 Dec;97(6):758-766.

doi: 10.1139/bcb-2018-0394. Epub 2019 Apr 3.

SARS Coronavirus Protein nsp1 Disrupts Localization of Nup93 From the Nuclear Pore Complex

Garret N Gomez  ^{1   1} , Fareeha Abrar  ^{1   1} , Maya P Dodhia  ^{1   1} , Fabiola G Gonzalez  ^{1   1} , Anita Nag  ¹

PMID: 30943371
DOI: 10.1139/bcb-2018-0394 

Severe acute respiratory syndrome coronavirus nonstructural protein 1 (nsp1) is a key factor in virus-induced down-regulation of host gene expression. In infected cells, nsp1 engages in a multipronged mechanism to inhibit host gene expression by binding to the 40S ribosome to block the assembly of translationally competent ribosome, and then inducing endonucleolytic cleavage and the degradation of host mRNAs. Here, we report a previously undetected mechanism by which nsp1 exploits the nuclear pore complex and disrupts the nuclear–cytoplasmic transport of biomolecules. We identified members of the nuclear pore complex  from the nsp1-associated protein assembly and found that the expression of nsp1 in HEK cells disrupts Nup93 localization around the nuclear envelope without triggering proteolytic degradation, while the nuclear lamina remains unperturbed. Consistent with its role in host shutoff, nsp1 alters the nuclear–cytoplasmic distribution of an RNA binding protein, nucleolin. Our results suggest that nsp1, alone, can regulate multiple steps of gene expression including nuclear–cytoplasmic transport.

Keywords: SARS-CoV, nsp1, Nup93, nuclear pore complex, NLS, immunofluorescence

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  • Download Figure
  • Download figure as PowerPoint slideDespite their huge size, NPCs are composed of only around 30 different nucleoporins. Because of the eight-fold symmetry of the pore, nucleoporins are present in 8, 16, 32 or more copies per NPC (for a review see Bilokapic and Schwartz, 2012; Grossman et al., 2012; Adams and Wente, 2013). They can be roughly categorized into those forming the scaffold of the pore, the structural nucleoporins, and those responsible for the transport functions of the NPC. The latter contain a high number of phenylalanine glycine (FG) repeats that form a meshwork via cohesive interactions within the pore, which in turn excludes most macromolecules from the passage but allows translocation of import and export receptor-bound targets (for a review see Fried and Kutay, 2003; Wente and Rout, 2010). Thus, these nucleoporins are important for both the exclusion and for the transport capabilities of the pore.
    The overall scaffolding structure of the NPC can be seen as a stack of three rings (Figure 1): The outer or cytoplasmic ring is connected to the cytoplasmic filaments whereas the nuclear ring is connected to the nuclear basket. Sandwiched between those two peripheral rings and located in the mid-plane of the nuclear envelope lays the spoke or inner ring. The inner ring is laterally linked to the pore membrane and connected to the central transport channel formed mostly by the FG-repeat-containing nucleoporins. Although NPC dimension and mass vary among organisms this overall structural arrangement, including the eight-fold symmetry, is conserved.
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