QKI6B mRNA levels are upregulated in schizophrenia and predict GFAP expression

Brain Res. 2017 Aug 15:1669:63-68. doi: 10.1016/j.brainres.2017.05.027. Epub 2017 May 25.

Abstract

Schizophrenia is a highly heritable disorder with a heterogeneous symptomatology. Research increasingly indicates the importance of the crucial and often overlooked glial perturbations within schizophrenia. Within this study, we examined an isoform of quaking (a gene encoding an RNA-binding protein that is exclusively expressed in glial cells), known as QKI6B, and a prototypical astrocyte marker, glial fibrillary acidic protein (GFAP), postulated to be under the regulation of QKI. The expression levels of these genes were quantified across post-mortem brain samples from 55 schizophrenic individuals, and 55 healthy controls, using real-time PCR. We report, through an analysis of covariance (ANCOVA) model, an upregulation of both QKI6B, and GFAP in the prefrontal cortex of brain samples of schizophrenic individuals, as compared to control samples. Previous research has suggested that the QKI protein directly regulates the expression of several genes through interaction with a motif in the target's sequence, termed the Quaking Response Element (QRE). We therefore examined if QKI6B expression can predict the outcome of GFAP, and several oligodendrocyte-related genes, using a multiple linear regression approach. We found that QKI6B significantly predicts the expression of GFAP, but does not predict oligodendrocyte-related gene outcome, as previously seen with other QKI isoforms.

Keywords: ANCOVA; Astrocytes; Glia; Regression; Schizophrenia; qPCR.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Astrocytes / metabolism
  • Female
  • Gene Expression / physiology
  • Glial Fibrillary Acidic Protein / metabolism*
  • Humans
  • Linear Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Oligodendroglia / metabolism
  • Prefrontal Cortex / metabolism*
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Schizophrenia / drug therapy
  • Schizophrenia / metabolism*
  • Young Adult

Substances

  • Glial Fibrillary Acidic Protein
  • QKI protein, human
  • RNA, Messenger
  • RNA-Binding Proteins