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Linkage, association and expression studies previously pointed to the human  QKI ,  KH domain containing ,  RNA-binding  ( QKI ) as a candidate gene for schizophrenia. Functional studies of the mouse orthologue  Qk  focused mainly on its role in oligodendrocyte development and myelination, while its function in astroglia remained unexplored. Here, we show that  QKI  is highly expressed in human primary astrocytes and that its splice forms encode proteins targeting different subcellular localizations. Uncovering the role of  QKI  in astrocytes is of interest in light of growing evidence implicating astrocyte dysfunction in the pathogenesis of several disorders of the central nervous system. We selectively silenced  QKI  splice variants in human primary astrocytes and used RNA sequencing to identify differential expression and splice variant composition at the genome-wide level. We found that an mRNA expression of  Glial fibrillary acidic protein  ( GFAP ), encoding a major component of astrocyte intermediate filaments, was down-regulated after  QKI7  splice variant silencing. Moreover, we identified a potential QKI-binding site within the 3′ untranslated region of human  GFAP.  This sequence was not conserved between mice and humans, raising the possibility that  GFAP  is a target for QKI in humans but not rodents. Haloperidol treatment of primary astrocytes resulted in coordinated increases in  QKI7  and  GFAP  expression. Taken together, our results provide the first link between  QKI  and  GFAP , two genes with alterations previously observed independently in schizophrenic patients. Our findings for  QKI , together with its well-known role in myelination, suggest that  QKI  is a hub regulator of glia function in humans.

RNA-binding protein QKI regulates Glial fibrillary acidic protein expression in human astrocytes