Distribution of SR protein exonic splicing enhancer motifs in human protein-coding genes

Jinhua Wang, Philip J. Smith, Adrian R. Krainer, Michael Q. Zhang

Research output: Contribution to journalArticlepeer-review

111 Scopus citations

Abstract

Exonic splicing enhancers (ESEs) are pre-mRNA cis-acting elements required for splice-site recognition. We previously developed a web-based program called ESEfinder that scores any sequence for the presence of ESE motifs recognized by the human SR proteins SF2/ASF, SRp40, SRp55 and SC35 (http://rulai.cshl.edu/tools/ESE/). Using ESEfinder, we have undertaken a large-scale analysis of ESE motif distribution in human protein-coding genes. Significantly higher frequencies of ESE motifs were observed in constitutive internal protein-coding exons, compared with both their flanking intronic regions and with pseudo exons. Statistical analysis of ESE motif frequency distributions revealed a complex relationship between splice-site strength and increased or decreased frequencies of particular SR protein motifs. Comparison of constitutively and alternatively spliced exons demonstrated slightly weaker splice-site scores, as well as significantly fewer ESE motifs, in the alternatively spliced group. Our results underline the importance of ESE-mediated SR protein function in the process of exon definition, in the context of both constitutive splicing and regulated alternative splicing.

Original languageEnglish (US)
Pages (from-to)5053-5062
Number of pages10
JournalNucleic acids research
Volume33
Issue number16
DOIs
StatePublished - 2005

Bibliographical note

Funding Information:
We thank Lawrence Chasin for kindly providing the pseudo exon database. This work was supported by NIH grants GM42699 to A.R.K. and HG01696/CA88351 to M.Q.Z, and by a postdoctoral fellowship from the US Army Medical Research and Matériel Command to P.J.S. The Open Access publication charges for this article were waived by Oxford University Press.

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