Thermodynamic modeling of donor splice site recognition in pre-mRNA.
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.
Garland
Jeffrey A
JA
Physics Department, Williams College, Williamstown, Massachusetts 01267, USA.
Aalberts
Daniel P
DP
D020029:Base Pairing; D003198:Computer Simulation; D007438:Introns; D008954:Models, Biological; D008956:Models, Chemical; D012322:RNA Precursors / Q000737:chemistry* / Q000378:metabolism; D022821:RNA Splice Sites; D012326:RNA Splicing; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000737:chemistry* / Q000378:metabolism; D017423:Sequence Analysis, RNA / Q000379:methods*; D017381:Spliceosomes / Q000737:chemistry* / Q000378:metabolism
D012322:RNA Precursors; D022821:RNA Splice Sites; D012333:RNA, Messenger; D017412:Ribonucleoprotein, U1 Small Nuclear