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Thermodynamic modeling of donor splice site recognition in pre-mRNA Jeffrey A. Garland and Daniel P. Aalberts*
 

Summary: Thermodynamic modeling of donor splice site recognition in pre-mRNA
Jeffrey A. Garland and Daniel P. Aalberts*
Physics Department, Williams College, Williamstown, Massachusetts 01267, USA
(Received 6 October 2003; published 26 April 2004; publisher error corrected 30 April 2004)
When eukaryotic genes are edited by the spliceosome, the first step in intron recognition is the binding of a
U1 small nuclear RNA with the donor 5 splice site. We model this interaction thermodynamically to identify
splice sites. Applied to a set of 65 annotated genes, our "finding with binding" method achieves a significant
separation between real and false sites. Analyzing binding patterns allows us to discard a large number of
decoy sites. Our results improve statistics-based methods for donor site recognition, demonstrating the promise
of physical modeling to find functional elements in the genome.
DOI: 10.1103/PhysRevE.69.041903 PACS number(s): 87.15. v, 87.10. e, 34.10. x, 82.60. s
The vast majority of bioinformatics methods treat nucleic
acids as simple strings of characters, abstracted of their com-
plex physical properties. To find biologically relevant areas
hidden in vast genomic sequences, such methods analyze
patterns of base frequencies extracted from large databases
of known signals. While such methods yield results for many
important problems, there are areas in which they have so far
proved insufficient.
One important example is RNA splicing. Before being

  

Source: Aalberts, Daniel P. - Department of Physics, Williams College

 

Collections: Physics