Control of alternative splicing by regulatory networks

• Applicant: Dr. Britta Hartmann
• Subject Area: Cell Biology
• Term: from 2007 to 2009
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 56644722

Recent evidence indicates that alternative splicing (AS) is a major contributor to the complexity of higher eukaryote proteomes and a relevant factor in an increasing number of pathologies. Paradoxically, however little is known about how regulatory networks influence this process. To address this question I decided to use novel genomic tools to explore the extent and biological impact of AS during sex determination and through the activation of signaling pathways in Drosophila. Sex differentiation in the fly has served as a prime example of AS regulation, with the protein Sex-lethal (SXL) regulating a handful of well characterized target genes. Unexpectedly, our genomic survey identified hundreds of sex-specific splicing changes, providing a new paradigm in which many new processes are regulated by known and new regulatory factors. In contrast to the well established roles of signaling on transcriptional regulation virtually nothing is known about how and to what extend they regulate gene expression at the post-transcriptional level. Our microarrays reveal that alternative splicing is regulated upon induction of the Insulin and Wingless pathways with interesting functional implications. These findings open up numerous opportunities to characterize the sequences, factors and molecular mechanisms involved in the regulation of alternative splicing by these regulating networks. I also plan to study the function of different isoforms at the molecular and the cellular level. Given the wealth of information about the components and functions of these pathways in fruitflies, it is expected that the project will contribute to our understanding of the impact and biological relevance of networks of alternative splicing regulation.

• DFG Programme: Research Fellowships
• International Connection: Spain
• Host: Professor Dr. Juan Valcárcel