Alternative splicing

altern_splicing_01Alternative splicing can lead to increased proteome variability and is thus a key to understand complexity in higher organisms. Members of the JCB investigate various aspects of alternative splicing:

Alternative splicing at tandem acceptors NAGNAG and donors GYNGYN:

Alternative 5’ splice sites GYNGYN and alternative 3’ splice sites NAGNAG (where N stands for A, G, C, and T, and Y means C or T) are frequent forms of alternative splice sites. We aim to find special patterns in nucleotide sequences causing the forms E(xonic), I(ntronic), or both. The Tandem Splice Site DataBase TassDB stores extensive data about alternative splice events at donors and acceptors, both confirmed and unconfirmed cases.

People:
  • Rolf Backofen (Albert-Ludwigs-Universität Freiburg)
  • Matthias Platzer (Leibniz Institute for Age Research, FLI)
  • Stefan Schuster (FSU, Dept. of Bioinformatics)

Alternative splicing at competitive tandem donor splice sites:

altern_splicing_02We also investigate the phenomena of short alternatively spliced eukaryotic transcripts with variations of length L < 20 between two consecutive donor splice sites. In particular alternative exons, which are spliced to the same downstream acceptor A5E, tend to show a strong bias on a length variation of 4 nucleotides, which define a splice site within a splice site. Such cases comprise about 8% of the observed A5E events and thus make up only one fourth of the observed 30% of short NAGNAG variations at alternative acceptor sites reported. Our results indicate about 85 % of these tetramer variations to be candidates for nonsense mediated mRNA decay. The remaining 15% constitute a special class of alternative splicing regulation that we are currently investigating.

People:
  • Dirk Holste (Austrian Research Centers, Vienna)
  • Matthias Platzer (Leibniz Institute for Age Research, FLI)
  • Stefan Schuster (FSU, Dept. of Bioinformatics)

Mutually exclusive splicing

altern_splicing_03In contrast to other alternative splicing subtypes, two (or more) processes must be executed or disabled coordinately in mutually exclusive splicing. The exchange of complete exons enables the encoding of a whole class of proteins with similar scaffold but different subdomains, and thus with specific functionality. Our data suggest that approximately 4% of human protein coding genes are affected by mutually exclusive splicing.

People:
  • Ralf Bortfeldt (Humboldt University of Berlin)
  • Dirk Holste (Austrian Research Centers, Vienna)
  • Stefan Schuster (FSU, Dept. of Bioinformatics)

Alternative splicing in the fungal domain

Alternative splicing occurs in some fungal species, but the distribution within the fungal domain and the effects on microbial lifestyle are unknown. Conceivably, the switch from mutualism to parasitism may involve regulated alternative splicing. We align transcript sequences (expressed sequence tags) to genome sequences of various fungi in order to identify alternatively spliced genes. These genes are placed in a cell biological context. This approach enables studies on conservation of the genes, phylogenetic distribution, and conclusions on evolution. Alternatively, splice variants are predicted ab initio: genomic DNA is searched for potential splicing signals. This method is used in particular for transcripts of rare developmental and other phenotypic stages. We develop an algorithm for classification of pseudo and real splice sites tailored to fungal sequence features.

People:
  • Matthias Platzer (Leibniz Institute for Age Research, FLI)
  • Stefan Schuster (FSU, Dept. of Bioinformatics)
  • Kerstin Voigt (FSU, Fungal Reference Center)