microRNAs and Schizophrenia

Over the past twenty years, our understanding of gene expression has grown tremendously. As is often the case, however, with that increased level of comprehension has come a realization that the process is even more complex than originally thought. Thus, the relatively simple model of mRNA being transcribed from DNA, then traveling to ribosomes where it is translated into proteins (with the help of tRNA and rRNA), is now thought to be just a rough summary of the process. A number of other molecules, such as transcription factors (TFs) and microRNAs (miRNAs), are also involved in the expression of genes.

TFs are proteins that bind to sections of DNA and control the transfer of genetic information from DNA to RNA. They are integral to development, management of the cell cycle, responding to environmental changes, and intercellular communication. miRNAs are small, single-stranded RNA molecules that are transcribed by DNA but not translated into proteins. They are complementary to a particular section of mRNA, and by binding to mRNA can suppress gene expression. TFs and miRNAs can control anywhere from dozens to hundreds of genes in the human genome, with some estimates being much higher.

Fully understanding the role of TFs and miRNAs is essential for uncovering the etiology of genetically based disorders. Recently researchers at Columbia University Medical Center (CUMC) found that changes in miRNA levels can result in cognitive and behavioral deficits. They believe miRNAs could be involved in the development of schizophrenia in humans.

In the past, a higher incidence of schizophrenia has been correlated with a deletion of a small part of chromosome 22, at a location designated as q11.2. One of the genes in that chromosomal section is called Dgcr8. It plays an integral role in miRNA production. Thus, the researchers at CUMC hypothesized that the absence of Dgcr8 and the resultant reduction in miRNAs might be part of the etiology of schizophrenia.

They engineered a strain of mice that lacked the Dgcr8 gene. As they predicted, the mice were found to exhibit the same behavioral and neuroanatomical deficits seen in people with schizophrenia.

While this is an important step in understanding one of the most perplexing disorders medicine has ever had to confront, it is not exactly heartening. miRNAs have widespread effects on gene expression throughout the brain. This may help to explain why schizophrenia has been so difficult to decipher, as it is probably the result of a number of genetic aberrations. Unfortunately, though, it is further indication that schizophrenia is very complex, and much more investigation will be needed to fully comprehend its origin.

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