@Article{Hiller:Huse:Szafranskzi:Phylo_wides_alter:2006,
  author =	 {M. Hiller and K. Huse and K. Szafranskzi and P. Rosenstiel 
                  and S. Schreiber and R. Backofen and M. Platzer},
  title =	 {Phylogenetically widespread alternative splicing at unusual 
                  {GYNGYN} donors},
  journal =	 {Genome Biol},
  year =	 {2006},
  volume =	 {7},
  number =	 {7},
  issn  =        {1465-6914},
  issn  =        {1465-6906},
  pages =	 {R65},
  user =	 {hiller},
  pmid =	 {16869967},
  abstract =	 {ABSTRACT: BACKGROUND: Splice donor sites have a highly 
                  conserved GT or GC dinucleotide and an extended intronic 
                  consensus sequence GTRAGT that reflects the sequence 
                  complementarity to the U1 snRNA. Here, we focus on unusual 
                  donor sites with the motif GYNGYN (Y stands for C or T; N 
                  stands for A,C,G, or T). RESULTS: While only one GY 
                  functions as a splice donor for the majority of these splice 
                  sites in human, we provide computational and experimental 
                  evidence that 110 (1.3%) allow alternative splicing at both 
                  GY donors. The resulting splice forms differ in only three 
                  nucleotides which results mostly in the insertion/deletion 
                  of one amino acid. However, we also report the insertion of 
                  a stop codon in four cases. Investigating what distinguishes 
                  alternatively from not alternatively spliced GYNGYN donors, 
                  we found differences in the binding to U1 snRNA, a strong 
                  correlation between U1 snRNA binding strength and the 
                  preferred donor, overrepresented sequence motifs in the 
                  adjacent introns, and a higher conservation of the exonic 
                  and intronic flanks between human and mouse. Extending our 
                  genome-wide analysis to seven other eukaryotic species, we 
                  found alternatively spliced GYNGYN donors in all species 
                  from mouse to C. elegans and even in A. thaliana. 
                  Experimental verification of a conserved GTAGTT donor of the 
                  STAT3 gene in human and mouse reveals a remarkably similar 
                  ratio of alternatively spliced transcripts in both species. 
                  CONCLUSION: In contrast to alternative splicing in general, 
                  GYNGYN donors in addition to NAGNAG acceptors enable subtle 
                  protein variations.}
}