Dysregulated Spliceosome Gene Expression May Be a Common Process in Brains of Neurological and Psychiatric Disorders

Alternative splicing (AS) contributes to the increased cellular and functional tissue complexity that is substantial in the brain. AS is tightly regulated because it is critical to many biological processes. Defective splicing is observed in several neurological and psychiatric disorders. While exonic mutations usually affect the splicing of an individual RNA, mutations in the splicing factors (components of spliceosome) frequently produce widespread disruption in the processing of many precursor-mRNAs. Thus, we tested the hypotheses that expression changes of spliceosome genes may be a common process and shared splicing pathways may be involved in complex polygenic brain disorders. We searched for expression changes of spliceosome-related genes (SGs) using a transcriptome database of several brain regions in 6 neurological and psychiatric disorders, namely Alzheimer’s disease, and autism spectrum, bipolar and major depressive disorder, Parkinson’s disease, and schizophrenia. Out of 255 SGs detected in brain, 138 showed excessive, significant changes in one or more of these disorders. Dysregulation of 10 SGs was shared in 4 disorders, and they were mostly downregulated. Six associated pathways were over-represented in all 6 disorders, including the major and the minor mRNA splicing pathways and RNA metabolism. Therefore, we found that aberrations in the mRNA splicing process may be a common trajectory to many complex brain disorders involving the spliceosome complex.