The role of non-coding RNAs in regulation of gene expression

The recent discovery of a wealth of short and long regulatory non-coding RNAs changed our view on the regulation of gene expression: they are involved at almost every level of gene expression, and their number and functional repertoire is constantly growing making them to one of the most abundant classes of regulatory molecules. Although their abundance and the known functions of individual examples highlight the importance of regulatory RNAs, their overall role in regulatory networks controlling gene expression during vertebrate development remains unclear. Recent advances in high-throughput sequencing make it possible to determine a genome-wide catalogue of non- coding RNAs in each species and to systematically study their regulation by selected transcription factors. This for the first time enables a comprehensive overview of the abundance, expression, and regulation of all non-coding RNAs and - for miRNAs - their regulatory targets, such that they can be integrated into regulatory networks. Here, I propose to determine a systematic catalogue of non-coding RNAs, their expression, and their regulatory regions in the zebrafish, an established vertebrate model organism. I further analyze the RNAs` gene regulation by two prominent neuronal transcription factors that are crucial for neurogenesis. This project will extend a neuronal core regulatory network that we previously established and in which both transcription factors regulate the neuronal miRNA miR-124 and are in turn regulated by miR-124. By systematically including additional genes and non- coding RNAs that are regulated by the transcription factors and in turn regulate neuronal genes, I expect to get a detailed picture on the regulatory connections in developing vertebrate nervous system, especially the contribution of novel non-coding RNAs. Network-level analyses will reveal to which extent regulatory network-motifs such as coherent and non-coherent feed-back or feed-forward loops are employed during neurogenesis and vertebrate development more general.