DFG SFB 604 INST 275/169-1
Alternative Splicing as a Modulator of Signal Transdruction
Description of the project:
Cells can change their splicing pattern in response to signals. Therefore, alternative splicing contributes to signal protein variability and information flow modulation, besides of posttranslational modification, differential gene expression and others.
Alternative splice variants of FGFR2. All these thirteen transcripts are confirmed by Reference Sequences (S: signal peptide, IG1, 2, 3: immunoglobulin domains, T: transmembrane domains, Boxes: exons, black: coding, grey: non-coding, white: exon¬skipping, red: prolonged exon, blue: shortened exon; drawing not to scale)
For this reason, we want to investigate the effect of alternative splicing on multifunctional signalling proteins, and determine regulatory mechanisms. We want to focus both on EST-based as well as on non-EST-based prediction methods for the identification of transcript variants, especially of those which are in the focus of the SFB. We will identify cis-acting elements, which are statistically linked to splicing events. These are, for instance, hexamer distribution patterns, conservation of exons and flanking introns in paralogs and orthologs, the score values of splice sites, as well as secondary structure elements in mRNA molecules. To find conserved secondary structure elements, we will employ and advance algorithms, currently under development. Modern learning techniques such as Bayesian networks, which we have used previously for the identification of transcription factor binding sites, will be applied for the prediction of transcript variants. The predicted splice forms will be validated by RT-PCR and sequencing. To gain more insight into the regulation of alternative splicing of signal proteins, we will cluster biologically related proteins to determine over- and underrepresented sequence or structure elements. In particular, we will focus on the functional effects of an alternative splicing phenomenon at NAGNAG acceptor sites, which was recently described by our group, on genes under investigation within the framework of the SFB. The general project aim is the extraction of splicing rules for classes of proteins, e.g. growth factor receptors, developmentally co-expressed genes or proteins with similar or equal splice pattern variations.
Additional information: http://www.sfb604.uni-jena.de/Project_B10_(Platzer)-highlight-Project_B10.html
contact person: Prof. Dr. Rolf Backofen
Start of project: 06.06.2005
End of project: 01.08.2009
Prof. Dr. Rolf Backofen
Actual Research Report