QKI-7 regulates expression of interferon-related genes in human astrocyte glioma cells.
<h4>Background</h4>The human QKI gene, called quaking homolog, KH domain RNA binding (mouse), is a candidate gene for schizophrenia encoding an RNA-binding protein. This gene was shown to be essential for myelination in oligodendrocytes. QKI is also highly expressed in astrocytes, but it...
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| Main Authors: | , , , , |
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| Format: | article |
| Language: | EN |
| Published: |
Public Library of Science (PLoS)
2010
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| Subjects: | |
| Online Access: | https://doaj.org/article/5731ee0d823345e5a308daa7c60dc01a |
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| Summary: | <h4>Background</h4>The human QKI gene, called quaking homolog, KH domain RNA binding (mouse), is a candidate gene for schizophrenia encoding an RNA-binding protein. This gene was shown to be essential for myelination in oligodendrocytes. QKI is also highly expressed in astrocytes, but its function in these cells is not known.<h4>Methods/principal findings</h4>We studied the effect of small interference RNA (siRNA)-mediated QKI depletion on global gene expression in human astrocyte glioma cells. Microarray measurements were confirmed with real-time quantitative polymerase chain reaction (qPCR). The presence of QKI binding sites (QRE) was assessed by a bioinformatic approach. Viability and cell morphology were also studied. The most significant alteration after QKI silencing was the decreased expression of genes involved in interferon (IFN) induction (P = 6.3E-10), including IFIT1, IFIT2, MX1, MX2, G1P2, G1P3, GBP1 and IFIH1. All eight genes were down-regulated after silencing of the splice variant QKI-7, but were not affected by QKI-5 silencing. Interestingly, four of them were up-regulated after treatment with the antipsychotic agent haloperidol that also resulted in increased QKI-7 mRNA levels.<h4>Conclusions/significance</h4>The coordinated expression of QKI-7 splice variant and IFN-related genes supports the idea that this particular splice variant has specific functions in astrocytes. Furthermore, a role of QKI-7 as a regulator of an inflammatory gene pathway in astrocytes is suggested. This hypothesis is well in line with growing experimental evidence on the role of inflammatory components in schizophrenia. |
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