Title

Studies on the expression and function of human microRNA, miR-1271

Date of Completion

January 2010

Keywords

Biology, Molecular|Biology, Genetics

Degree

Ph.D.

Abstract

The mechanisms underlying the genesis of psychiatric disorders in humans are largely unknown. A current hypothesis suggests that these disorders might be caused partly by alterations in the mechanisms that control the spatial and temporal pattern of human gene expression. Certain animal behavior genes may be involved in the development of psychiatric disorders; therefore, this thesis investigates the mechanisms that may control their expression in the human central nervous system. Our initial findings show that common human polymorphisms in the mRNA of genes related to animal behavior alter microRNA-directed regulation of gene expression. These variants are not only functional, but are clinically significant, in that they predict human behavior phenotypes. We have found that a microRNA target polymorphism in the serotonin receptor 1B (HTR1B) mRNA, a gene implicated in animal aggression, predicts aggressive phenotypes in college-aged students. Given the clinical significance of the polymorphic element from the HTR1B mRNA, we have explored the mechanisms and factors that target it to control gene expression. In doing so, we have characterized the function of a non-conserved microRNA gene, miR-1271 that is expressed specifically in the human nervous system and regulates genes involved in cell signaling. The novel findings presented in this thesis point towards an important and expanding role for non-coding RNAs in the biology of neurological and psychiatric disorders. ^