Intrinsic differences between authentic and cryptic 5 ' splice sites

Roca, X., Sachidanandam, R., Krainer, A. R. (November 2003) Intrinsic differences between authentic and cryptic 5 ' splice sites. Nucleic Acids Research, 31 (21). pp. 6321-6333. ISSN 0305-1048

[img]
Preview
PDF (Paper)
Sachidanandam and Krainer Nucleic Acids Research 2003.pdf - Published Version

Download (225Kb) | Preview
URL: http://www.ncbi.nlm.nih.gov/pubmed/14576320
DOI: 10.1093/nar/gkg830

Abstract

Cryptic splice sites are used only when use of a natural splice site is disrupted by mutation. To determine the features that distinguish authentic from cryptic 5' splice sites (5'ss), we systematically analyzed a set of 76 cryptic 5'ss derived from 46 human genes. These cryptic 5'ss have a similar frequency distribution in exons and introns, and are usually located close to the authentic 5'ss. Statistical analysis of the strengths of the 5'ss using the Shapiro and Senapathy matrix revealed that authentic 5'ss have significantly higher score values than cryptic 5'ss, which in turn have higher values than the mutant ones. beta-Globin provides an interesting exception to this rule, so we chose it for detailed experimental analysis in vitro. We found that the sequences of the beta-globin authentic and cryptic 5'ss, but not their surrounding context, determine the correct 5'ss choice, although their respective scores do not reflect this functional difference. Our analysis provides a statistical basis to explain the competitive advantage of authentic over cryptic 5'ss in most cases, and should facilitate the development of tools to reliably predict the effect of disease-associated 5'ss-disrupting mutations at the mRNA level.

Item Type: Paper
Uncontrolled Keywords: DYSTROPHIC EPIDERMOLYSIS-BULLOSA ACUTE INTERMITTENT PORPHYRIA SINGLE-POINT MUTATION MESSENGER-RNA DONOR-SITE IN-VITRO U1 SNRNA NULL ALLELE OSTEOGENESIS IMPERFECTA CAENORHABDITIS-ELEGANS
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > splice site
CSHL Authors:
Communities: CSHL labs > Krainer lab
CSHL labs > Sachidanandam lab
Depositing User: Matt Covey
Date: November 2003
Date Deposited: 02 Apr 2013 15:08
Last Modified: 02 Apr 2013 15:08
PMCID: PMC275472
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27997

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving