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Intrinsic differences between authentic and cryptic 5' splice sites.
Nucleic Acids Res. 2003 Nov 01; 31(21):6321-33.NA

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.

Authors+Show Affiliations

Cold Spring Harbor Laboratory, PO Box 100, Cold Spring Harbor, NY 11724, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

14576320

Citation

Roca, Xavier, et al. "Intrinsic Differences Between Authentic and Cryptic 5' Splice Sites." Nucleic Acids Research, vol. 31, no. 21, 2003, pp. 6321-33.
Roca X, Sachidanandam R, Krainer AR. Intrinsic differences between authentic and cryptic 5' splice sites. Nucleic Acids Res. 2003;31(21):6321-33.
Roca, X., Sachidanandam, R., & Krainer, A. R. (2003). Intrinsic differences between authentic and cryptic 5' splice sites. Nucleic Acids Research, 31(21), 6321-33.
Roca X, Sachidanandam R, Krainer AR. Intrinsic Differences Between Authentic and Cryptic 5' Splice Sites. Nucleic Acids Res. 2003 Nov 1;31(21):6321-33. PubMed PMID: 14576320.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Intrinsic differences between authentic and cryptic 5' splice sites. AU - Roca,Xavier, AU - Sachidanandam,Ravi, AU - Krainer,Adrian R, PY - 2003/10/25/pubmed PY - 2003/12/10/medline PY - 2003/10/25/entrez SP - 6321 EP - 33 JF - Nucleic acids research JO - Nucleic Acids Res. VL - 31 IS - 21 N2 - 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. SN - 1362-4962 UR - https://www.unboundmedicine.com/medline/citation/14576320/Intrinsic_differences_between_authentic_and_cryptic_5'_splice_sites_ L2 - https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkg830 DB - PRIME DP - Unbound Medicine ER -