Expression of <i>Hqk</i> Encoding a KH RNA Binding Protein Is Altered in Human Glioma

Li, Zheng Zhe; Kondo, Tatsuya; Murata, Tomoaki; Ebersole, Thomas A.; Nishi, Toru; Tada, Kohei; Ushio, Yukitaka; Yamamura, Ken Ichi; Abe, Kuniya

doi:10.1111/j.1349-7006.2002.tb01255.x

Cited by 55 publications

(49 citation statements)

References 38 publications

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“…Lastly, multiple probe sets for QKI identified a common pattern of downregulated expression in depressed suicides across all four brain regions studied. The QKI gene 37 is the human homologue of the mouse QKI, affected in the 'Quaking' mouse that displays severe dysmyelination of the CNS. The QKI gene product appears to function as an RNA-binding protein, interacting through KH domains with numerous transcripts controlling oligodendrocyte fate specification and myelin component metabolism.…”

Section: Discussionmentioning

confidence: 99%

Altered expression of genes involved in ATP biosynthesis and GABAergic neurotransmission in the ventral prefrontal cortex of suicides with and without major depression

et al. 2007

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The prefrontal cortex is believed to play a major role in depression and suicidal behavior through regulation of cognition, memory, recognition of emotion, and anxiety-like states, with numerous post-mortem studies documenting a prefrontal serotonergic dysregulation considered to be characteristic of depressive psychopathology. This study was carried out to detect changes in gene expression associated with both suicide and major depression using oligonucleotide microarrays (Affymetrix HG-U133 chip set) summarizing expression patterns in primarily ventral regions of the prefrontal cortex (BA44, 45, 46 and 47). A total of 37 male subjects were included in this study, of which 24 were suicides (depressed suicides = 16, nondepressed suicides = 8) and 13 were matched controls. All subjects were clinically characterized by means of psychological autopsies using structured interviews. Unique patterns of differential expression were validated in each of the cortical regions evaluated, with group-specific changes highlighting the involvement of several key neurobiological pathways that have been implicated in both suicide and depression. An overrepresentation of factors involved in cell cycle control and cell division (BA44), transcription (BA44 and 47) and myelination (BA46) was seen in gene ontology analysis of differentially expressed genes, which also highlights changes in the expression of genes involved in ATP biosynthesis and utilization across all areas. Gene misexpression in BA46 was most pronounced between the two suicide groups, with many significant genes involved in GABAergic neurotransmission. The pronounced misexpression of genes central to GABAergic signaling and astrocyte/ oligodendrocyte function provides further support for a central glial pathology in depression and suicidal behavior.

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Section: Discussionmentioning

confidence: 99%

Altered expression of genes involved in ATP biosynthesis and GABAergic neurotransmission in the ventral prefrontal cortex of suicides with and without major depression

et al. 2007

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“…Mutations within the gene in its regulatory elements or on other genes regulated by QKI may lead to disease manifestation in humans. 143 The involvement of the functional variants of the QKI gene in the increase of susceptibility to schizophrenia is further corroborated by its locus; it maps on chromosome 6q25-6q27, a region that is strongly associated with vulnerability to the disorder. 97,144 The role of these genes in the susceptibility to schizophrenia derives added weight from a number of genetic linkage studies that confirm linkage of the disease to specific loci for these genes.…”

Section: Cnp 17q21mentioning

confidence: 98%

The myelin-pathogenesis puzzle in schizophrenia: a literature review

2007

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Schizophrenia is a serious and disabling mental disorder with symptoms such as auditory hallucinations, disordered thinking and delusions, avolition, anhedonia, blunted affect and apathy. In this review article we seek to present the current scientific findings from linkage studies and susceptible genes and the pathophysiology of white matter in schizophrenia. The article has been reviewed in two parts. The first part deals with the linkage studies and susceptible genes in schizophrenia in order to have a clear-cut picture of the involvement of chromosomes and their genes in schizophrenia. The genetic linkage results seem to be replicated in some cases but in others are not. From these results, we cannot draw a fine map to a single locus or gene, leading to the conclusion that schizophrenia is not caused by a single factor/gene. In the second part of the article we present the oligodendrocyte-related genes that are associated with schizophrenia, as we hypothesize a potential role of oligodendrocyte-related genes in the pathology of the disorder.

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“…A study reported the loss of QKI mRNA expression in human glioblastomas and not other tumors (54). The qkI gene locus is located on 6q26-q27, a region commonly associated with abnormalities in human malignancies, including astroctytic tumors (55).…”

Section: Discussionmentioning

confidence: 99%

The QKI-5 and QKI-6 RNA Binding Proteins Regulate the Expression of MicroRNA 7 in Glial Cells

Wang

Vogel

et al. 2013

Molecular and Cellular Biology

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The quaking (qkI) gene encodes 3 major alternatively spliced isoforms that contain unique sequences at their C termini dictating their cellular localization. QKI-5 is predominantly nuclear, whereas QKI-6 is distributed throughout the cell and QKI-7 is cytoplasmic. The QKI isoforms are sequence-specific RNA binding proteins expressed mainly in glial cells modulating RNA splicing, export, and stability. Herein, we identify a new role for the QKI proteins in the regulation of microRNA (miRNA) processing. We observed that small interfering RNA (siRNA)-mediated QKI depletion of U343 glioblastoma cells leads to a robust increase in miR-7 expression. The processing from primary to mature miR-7 was inhibited in the presence QKI-5 and QKI-6 but not QKI-7, suggesting that the nuclear localization plays an important role in the regulation of miR-7 expression. The primary miR-7-1 was bound by the QKI isoforms in a QKI response element (QRE)-specific manner. We observed that the pri-miR-7-1 RNA was tightly bound to Drosha in the presence of the QKI isoforms, and this association was not observed in siRNA-mediated QKI or Drosha-depleted U343 glioblastoma cells. Moreover, the presence of the QKI isoforms led to an increase presence of pri-miR-7 in nuclear foci, suggesting that pri-miR-7-1 is retained in the nucleus by the QKI isoforms. miR-7 is known to target the epidermal growth factor (EGF) receptor (EGFR) 3= untranslated region (3=-UTR), and indeed, QKI-deficient U343 cells had reduced EGFR expression and decreased ERK activation in response to EGF. Elevated levels of miR-7 are associated with cell cycle arrest, and it was observed that QKI-deficient U343 that harbor elevated levels of miR-7 exhibited defects in cell proliferation that were partially rescued by the addition of a miR-7 inhibitor. These findings suggest that the QKI isoforms regulate glial cell function and proliferation by regulating the processing of certain miRNAs.

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Expression of Hqk Encoding a KH RNA Binding Protein Is Altered in Human Glioma

Cited by 55 publications

References 38 publications

Altered expression of genes involved in ATP biosynthesis and GABAergic neurotransmission in the ventral prefrontal cortex of suicides with and without major depression

Altered expression of genes involved in ATP biosynthesis and GABAergic neurotransmission in the ventral prefrontal cortex of suicides with and without major depression

The myelin-pathogenesis puzzle in schizophrenia: a literature review

The QKI-5 and QKI-6 RNA Binding Proteins Regulate the Expression of MicroRNA 7 in Glial Cells

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