Human QKI, a potential regulator of mRNA expression of human oligodendrocyte-related genes involved in schizophrenia.
The quaking viable mouse mutation (qk(v)) is a deletion including the 5' regulatory region of the quaking gene (Qki), which causes body tremor and severe dysmyelination in mouse. The function of the human quaking gene, called quaking homolog KH domain RNA-binding (mouse) (QKI), is not well known. We have previously shown that QKI is a new candidate gene for schizophrenia. Here we show that human QKI mRNA levels can account for a high proportion (47%) of normal interindividual mRNA expression variation (and covariation) of six oligodendrocyte-related genes (PLP1, MAG, MBP, TF, SOX10, and CDKN1B) in 55 human brain autopsy samples from individuals without psychiatric diagnoses. In addition, the tightly coexpressed myelin-related genes (PLP1, MAG, and TF) have decreased mRNA levels in 55 schizophrenic patients, as compared with 55 control individuals, and most of this difference (68-96%) can be explained by variation in the relative mRNA levels of QKI-7kb, the same QKI splice variant previously shown to be down-regulated in patients with schizophrenia. Taken together, our results suggest that QKI levels may regulate oligodendrocyte differentiation and maturation in human brain, in a similar way as in mouse. Moreover, we hypothesize that previously observed decreased activity of myelin-related genes in schizophrenia might be caused by disturbed QKI splicing.
Aberg
Karolina
K
Department of Evolution, Genomics and Systematics, Uppsala University, SE-75236 Uppsala, Sweden.
Saetre
Peter
P
Jareborg
Niclas
N
Jazin
Elena
E
D000818:Animals; D001344:Autopsy; D001483:Base Sequence; D001665:Binding Sites; D017124:Conserved Sequence; D005786:Gene Expression Regulation; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009185:Myelin Proteins / Q000235:genetics; D009186:Myelin Sheath / Q000235:genetics; D009836:Oligodendroglia / Q000378:metabolism*; D016366:Open Reading Frames / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D016415:Sequence Alignment; D014158:Transcription, Genetic / Q000235:genetics
D009185:Myelin Proteins; C490832:QKI protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins