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Stem cell research is revolutionizing the way scientists think about mammalian development. It is a field full of promise to treat many debilitating and degenerative diseases. Regulation of stem cells by transcription factors that bind to specific DNA loci to control gene regulatory networks have been well studied in various stem cell populations. However, the mechanisms by which the regulation of post-transcriptional RNA processing influences the timely, highly specialized differentiation of stem cells are not well understood. Only recently have researchers started focusing attention on the importance of RNA regulation in the control of gene expression and, thus, to impact human health. RNA binding proteins (RBPs) bind to and regulate RNA metabolism at multiple levels from processing within the nucleus, nuclear export, and transport to organelles within the cytoplasm. In addition, RBPs can regulate RNA stability and protein translation. Techniques to study and identify the RNA substrates regulated by RNA binding proteins have only recently been developed within the last decade, with the availability of high-throughput sequencing revolutionizing established techniques, enabling transcriptome-wide views of RNA biology. My dissertation research focuses on the function of the IGF2BP/IMP family of RNA binding proteins. In particular, I have investigated the role of IGF2BP1/IMP1, in early human development using human embryonic stem cells (hESCs) as a model system. I have used CLIP-seq to identify the endogenous targets of IMP1 in hESCs and have determined the mechanism of regulation for the novel target ITGB5. Additionally, I have uncovered a role for IMP1 in early neural progenitor cell populations and in localization of target RNAs. Ongoing studies comparing and contrasting the various targets and functions of IMP1 and IMP2 in hESCs at the genome-wide level will pave the way for future investigators to dissect the individual functions for each of these RBPs. This work will provide a resource for those aiming to understand the mechanisms of how these proteins control their target RNAs during development and tumorigenesis |
