Molecular regulation of mRNA stability and translation

The flow of information from DNA to RNA to protein is a tightly regulated process, which ultimately determines the functional properties that each cell will possess. Defects in any of the multiple regulatory mechanisms that ensure that proper amounts of each protein are produced within a particular cell, may lead to dysregulation of cellular processes and disease. This dissertation will deal with 2 different projects. The common theme between these projects is that we studied post-transcriptional regulation of gene expression at the level of messenger RNA (mRNA), and in both studies we took advantage of genome-wide sequencing techniques to develop insights and novel hypothesis within the realm of neurobiology. Briefly, the first project is a study of the role of Cyfip1, a neuropsychiatric disease risk gene, in regulating the translation of its mRNA partners. We show that deletion and over-expression of Cyfip1 in the mouse brain, leads to diametric changes in protein translation of NMDAR subunits and postsynaptic components, and has consequences in behavior within these mouse models. The second study is an exploration of the role of m6A epitranscriptional modification in the regulation of cortical neurogenesis in-vivo, where we identified a critical and conserved role of m6A in the temporal control of mammalian cortical neurogenesis