Mechanisms contributing to RNA localization and translation: study of neuronal zipcodes in primary cortical neurons, and translational changes in neurodegeneration

Abstract

The regulation of gene expression in terms of space and time is governed by the distribution of RNA and proteins within a cell. This tightly controlled regulation is necessary for mediating cellular development and function. The localization of RNA is also a highly controlled process that is influenced by specific cis and trans-acting elements. In polarized cells, such as neurons, the localization of transcripts towards axons and dendrites (neurites) enables the immediate and efficient local synthesis of proteins in response to external stimuli. This thesis focuses on the examination of the cis-elements, or "zipcodes," that contribute to the localization of RNA towards the neurites and the translational defects that result in the peripheral neuropathy Charcot-Marie-Tooth (CMT) disease.