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Nucleic Acids Res. 2011 Mar;39(6):2344-56. doi: 10.1093/nar/gkq1046. Epub 2010 Nov 10.

An SF1 affinity model to identify branch point sequences in human introns.

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  • 1Department of Biochemistry and Biophysics, University of California, San Francisco, USA.

Abstract

Splicing factor 1 (SF1) binds to the branch point sequence (BPS) of mammalian introns and is believed to be important for the splicing of some, but not all, introns. To help identify BPSs, particularly those that depend on SF1, we generated a BPS profile model in which SF1 binding affinity data, validated by branch point mapping, were iteratively incorporated into computational models. We searched a data set of 117,499 human introns for best matches to the SF1 Affinity Model above a threshold, and counted the number of matches at each intronic position. After subtracting a background value, we found that 87.9% of remaining high-scoring matches identified were located in a region upstream of 3'-splice sites where BPSs are typically found. Since U2AF65 recognizes the polypyrimidine tract (PPT) and forms a cooperative RNA complex with SF1, we combined the SF1 model with a PPT model computed from high affinity binding sequences for U2AF65. The combined model, together with binding site location constraints, accurately identified introns bound by SF1 that are candidates for SF1-dependent splicing.

PMID:
21071404
[PubMed - indexed for MEDLINE]
PMCID:
PMC3064769
Free PMC Article

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