Disease relevance of QKI

• We have used a gain-of-function approach with the ectopic expression of the separate QKI isoforms using adenoviruses and retroviruses to determine their separate roles in cell fate and myelination [1].
• Expression of Hqk encoding a KH RNA binding protein is altered in human glioma [2].
• Analysis of primary tumors demonstrated a high incidence of expression alterations of Hqk in gliomas (30%; 6/20), but not in other tumors such as schwannomas (0/3), or meningiomas (0/8) [2].

High impact information on QKI

• Disruption of the QKI nucleocytoplasmic equilibrium in oligodendrocytes results in nuclear and perikaryal retention of the MBP mRNAs and lack of export to cytoplasmic processes, as it occurs in qk(v) mice [3].
• We show that the QKI RNA binding proteins regulate the nuclear export of MBP mRNAs [3].
• QKI Binds MAP1B mRNA and Enhances MAP1B Expression during Oligodendrocyte Development [4].
• Its product, QKI, is an RNA-binding protein belonging to a growing protein family called STAR (signal transduction and activator of RNA) [5].
• This suggests that the QUA1 domain is responsible for QKI dimerization [5].

Biological context of QKI

• QKI gene expression deficits detected by microarray were validated by qPCR in the cingulate cortex, where the expression of isoforms QKI-5, QKI-6, and QKI-7 were profoundly perturbed in schizophrenia [6].
• The Hqk gene contains 8 exons spanning a approximately 200 kb genomic region, and generating at least four alternatively spliced transcripts, Hqk-5, Hqk-6, Hqk-7 and Hqk-7B, of which Hqk-7 is abundantly expressed in brain [2].
• The human quaking gene, Hqk, maps to 6q25-q26, where cytogenetic alterations associated with a variety of human malignancies, including gliomas have been reported [2].

Anatomical context of QKI

• RESULTS: Expression of QKI mRNA was decreased in seven cortical regions and the hippocampus in the schizophrenia subjects [6].
• Given the role of QKI in determination of oligodendrocyte fate, these results not only confirm oligodendrocyte-related gene expression abnormalities in schizophrenia but suggest that the physiology of glial progenitor cells may be altered in schizophrenia [6].
• Herein, we discuss the recent advances in characterizing the QKI KH-type proteins as glial cell fate and myelin egulators [1].

Physical interactions of QKI

• In addition, we found posttranscriptional regulation of MAP1B mRNA by the selective RNA-binding protein QKI in oligodendroglia [4].

Other interactions of QKI

• The mRNA levels of QKI and its isoforms were then measured in a larger cohort by using quantitative real-time polymerase chain reaction (qPCR) in the cingulate cortex of schizophrenia subjects and matched comparison subjects [6].

Analytical, diagnostic and therapeutic context of QKI

• The two family based studies suggest that there may be functional variants of the QKI gene that increase the susceptibility of schizophrenia in northern Sweden, whereas the case-control study suggest that splicing of the gene may be disturbed in schizophrenic patients from other geographical origins [7].

References