Cited by 208Schizophrenia research and treatmentRNA Research and SplicingGenetics and Neurodevelopmental Disorders

Human QKI, a potential regulator of mRNA expression of human oligodendrocyte-related genes involved in schizophrenia

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Åberg, Karolina, Saetre, Peter, Jareborg, Niclas, Jazin, Elena·2006·Proceedings of the National Academy of Sciences

Abstract

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.

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Crossref · 10.1073/pnas.0601213103

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Authors
Åberg, K., Saetre, P., Jareborg, N., & Jazin, E.
Affiliations
  • Uppsala University (SE)
  • AstraZeneca (Sweden) (SE)
Venue
Proceedings of the National Academy of Sciences
Published
2006-05-09
Volume
103
Issue
19
Pages
7482-7487
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W1987002276
Cited by
208
References
35
Citations by year
2026: 2 · 2025: 5 · 2024: 10 · 2023: 7 · 2022: 15 · 2021: 6 · 2020: 10 · 2019: 11 · 2018: 11 · 2017: 14 · 2016: 10 · 2015: 9 · 2014: 10 · 2013: 10 · 2012: 10
FWCI
8.37
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
QKI, schizophrenia, oligodendrocytes, myelin genes, PLP1, myelin basic protein, myelin-associated glycoprotein, SOX10, p27, TF, gene expression variation, oligodendrocyte differentiation, dysmyelination, candidate genes
MeSH terms
Animals, Autopsy, Base Sequence, Binding Sites, Gene Expression Regulation, Humans, Molecular Sequence Data, Myelin Proteins, Myelin Sheath, Oligodendroglia, RNA, Messenger, Schizophrenia, Transcription, Genetic, Genetic Variation, Open Reading Frames, Sequence Alignment, RNA-Binding Proteins, Conserved Sequence

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