Intrinsic differences between authentic and cryptic 5' splice sites.

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.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Roca X,Sachidanandam R,Krainer AR

doi

10.1093/nar/gkg830

keywords:

subject

Has Abstract

pub_date

2003-11-01 00:00:00

pages

6321-33

issue

21

eissn

0305-1048

issn

1362-4962

journal_volume

31

pub_type

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