Importin-7 mediates nuclear trafficking of DNA in mammalian cells.
Bottom Line: Poor DNA nuclear import in cells depleted of imp7 directly correlated with lower gene expression levels in these cells compared to controls.Inefficient nuclear import of transfected DNA induced greater upregulation of the interferon pathway, suggesting that rapid DNA nuclear import may prevent uncontrolled activation of the innate immune response.Our results provide evidence that imp7 is a non-redundant component of an intrinsic pathway in mammalian cells for efficient accumulation of exogenous and endogenous DNA in the nucleus, which may be critical for the exchange of genetic information between mitochondria and nuclear genomes and to control activation of the innate immune response.
Affiliation: The Advanced Centre for Biochemical Engineering, University College London, Torrington Place, London, WC1E 7JE, UK.Show MeSH
Mentions: IFIT2 is an example of a type I IFN induced gene. We also examined the expression of class I MHC on the surface of the HeLa cells, because upregulation of class I MHC is another well-established response to type I IFNs. Control or Imp7 knockdown clones were transfected with pHR plasmid (using Fugene rather than PLL in order to increase transfection efficiency to a level which could be quantified by flow cytometry). Despite a significant background of MHC-I expression in all the cell lines, plasmid transfection reproducibly increased MHC class I expression in the two knockdown clones, but not in control or back complemented HeLa clones (Figure 7). IFN-β induced expression of MHC class I in both control and imp7 knockdown clones equally, indicating that depletion of imp7 did not interfere with the IFN response in these experimental conditions.
Affiliation: The Advanced Centre for Biochemical Engineering, University College London, Torrington Place, London, WC1E 7JE, UK.