Regulation of gene expression by TRA2-beta1

• Applicant: Professor Dr. Stefan Stamm
• Subject Area: Cell Biology
• Term: from 2005 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5451190

Alternative pre-mRNA splicing is one of the most abundantly used postranscriptional mechanism, which increases the number of proteins from the surprisingly low number of ca. 25,000 human genes. Although at least 74% of all human genes are alternatively spliced, it is unclear how a limited number of splicing factors -estimated to be about 200- controls alternative splice site selection. It is also unclear how splice site selection is altered in response to cellular stimulation. A single factor can control numerous target genes in a physiologically meaningful way. For example, in drosophila, the factor dtra2 controls at least 6 genes that all determine the sex of flies. We therefore want to test the hypothesis that the human splicing factor htra2-beta1 regulates a physiologically related set of genes by determining its target genes. To investigate how cellular signals influence splice site selection, we will determine kinases acting on tra2-beta1 and analyze the influence of phosphorylation on the formation of ribonuclear and cytosol where it accumulates under pathophysiological conditions. We will test whether tra2-beta1 regulates their translation, RNA stability or RNA export. Together, these experiments will show how an evolutionary highly conserved protein orchestrates posttranscriptional events to regulate gene expression.

• DFG Programme: Research Grants