[
International Worm Meeting,
2021]
Alternative splicing is a major contributor of cellular complexity and it is regulated in a highly tissue- and context-dependent manner. Many studies have focused on investigating the major regulators of alternative splicing, cis-elements and trans-factors, by learning predictive models on native sequences and through in vitro studies or cell-based screens. However, investigating the roles of a multitude of these factors in a more systematic manner in vivo is challenging and remains an understudied area. The goal of our project is to develop a high-throughput system to investigate the different cis-elements and trans-factors controlling alternative splicing in different contexts in vivo. To this end, we have employed a parallel reporter assay (PRA) in Caenorhabditis elegans using reporters to monitor alternative splicing patterns in specific cell and tissue types. We have used this approach to screen thousands of random sequences and have identified 469 putative intronic cis elements enhancing or repressing alternative splicing patterns in neuronal tissue. I will further extend this approach to identify sequence features and trans-factors associated with other tissue- as well as single neuron-biased splicing patterns. Together, this work will provide insight into the mechanisms governing tissue and cell-specific splicing patterns in vivo.