MicroRNA in schizophrenia: Genetic and expression analysis of miR-130b (22q11)

Abstract

MicroRNAs (miRNAs) are a class of small regulatory RNAs that control a level of expression of protein encoding genes. Their role in brain pathologies is unknown. We made a first attempt to carry out a genetic study coupled with gene expression analysis of microRNA in human neuropsychiatric pathology. Presumably, at least one third of known miRNA genes are expressed in the brain. Mutations disrupting MECP2 protein lead to abnormal development of the brain and resulting behavior. MiR-130b expressed in the brain and potentially targeting MECP2 is located in the susceptibility locus for schizophrenia (22q11). We performed a comparative analysis of the expression of miR-130b in 24 brain neocortex samples from schizophrenic and normal individuals. The stability and effective detection of mature microRNA in postmortem tissues using Real-time PCR have been shown. Screening for mutations has identified a population polymorphism in the 5 -upstream miR-130b gene region containing DNA elements for putative transcription factors. Genetic association analysis of 300 schizophrenia and 316 normal control individuals revealed no statistically significant association of any of the miR-130b allelic variants with schizophrenia. The data demonstrated feasibility and perspective of convergent genetic and expression analysis of human microRNA genes in testing their role in human diseases.

microRNA-Seq reveals cocaine-regulated expression of striatal microRNAs

“…Recent studies have demonstrated the importance of miRNAs in the pathophysiology of several neuropsychiatric disorders and mental retardation syndromes (Conrad et al 2010;Sulzer 2011), including schizophrenia (Burmistrova et al 2007;Beveridge et al 2010;Moreau et al 2011;Santarelli et al 2011), bipolar disorder, Fragile X mental retardation (Edbauer et al 2010;Krol et al 2010;Wulff et al 2011), Rett syndrome (Wu et al 2010), Alzheimer's disease, Parkinson's disease (Junn et al 2009), and Huntington's disease (Martí et al 2010). A number of the cocaine-responsive miRNAs identified in this study are important in controlling dendritic morphology; these miRNAs, and many others, may contribute to long-lasting forms of drugmediated synaptic plasticity through control of regulatory Lugli et al 2008 (adult mouse cortex and hippocampus; measured by microarray) with RNA-Seq data (adult mouse striatum) from these experiments (Lugli et al 2008).…”

Rett Syndrome and MeCP2

“…In schizophrenic brain neocortex, miR130b has been shown to target 3′UTR of MECP2 (Burmistrova et al 2007). Both miR-155 and miR-802 can downregulate MeCP2 expression in Downs Syndrome brains and thereby cause altered expression of MeCP2 target genes Creb1 and Mef2c (Kuhn et al 2010).…”

MicroRNAs in learning, memory, and neurological diseases: Figure 1.

“…Stark et al (2008) generated a mouse model with a deletion of the corresponding human chromosomal segment, which includes nearly all the functional genes affected by the human 22q11.2 deletion, including the miRNA processing protein, DGCR8 (Stark et al 2008). These mice exhibit abnormal microRNA biogenesis due to the loss of DGCR8 function, and the subsequent impaired expression of a subset of miRNAs, including miR-134 (Burmistrova et al 2007), which is directly implicated in learning and memory (Gao et al 2010). The behavioral defects displayed by these mice are accompanied by abnormal dendrite and spine morphogenesis, which may result from dysregulated miRNA expression.…”