Identification of functional exonic splicing enhancer motifs recognized by individual SR proteins

Liu, H. X., Zhang, M., Krainer, A. R. (July 1998) Identification of functional exonic splicing enhancer motifs recognized by individual SR proteins. Genes & Development, 12 (13). pp. 1998-2012. ISSN 0890-9369

[img]
Preview
PDF (Paper)
Krainer and Zhang Genes and Development 1998.pdf - Published Version

Download (1143Kb) | Preview
URL: http://www.ncbi.nlm.nih.gov/pubmed/9649504
DOI: 10.1101/gad.12.13.1998

Abstract

Using an in vitro randomization and functional selection procedure, we have identified three novel classes of exonic splicing enhancers (ESEs) recognized by human SF2/ASF, SRp40, and SRp55, respectively. These ESEs are functional in splicing and are highly specific. For SF2/ASF and SRp55, in most cases, only the cognate SR protein can efficiently recognize an ESE and activate splicing. In contrast, the SRp40-selected ESEs can function with either SRp40 or SRp55, but not with SF2/ASF. UV cross-linking/competition and immunoprecipitation experiments showed that SR proteins recognize their cognate ESEs in nuclear extract by direct and specific binding. A motif search algorithm was used to derive consensus sequences for ESEs recognized by these SR proteins. Each SR protein yielded a distinct 5- to 7-nucleotide degenerate consensus. These three consensus sequences occur at higher frequencies in exons than in introns and may thus help define exon-intron boundaries. They occur in clusters within regions corresponding to naturally occurring, mapped ESEs. We conclude that a remarkably diverse set of sequences can function as ESEs. The degeneracy of these motifs is consistent with the fact that exonic enhancers evolved within extremely diverse protein coding sequences and are recognized by a small number of SR proteins that bind RNA with limited sequence specificity.

Item Type: Paper
Uncontrolled Keywords: SR proteins exonic splicing enhancers SF2/ASF RNA sequence motifs SELEX pre-messenger-rna small nuclear ribonucleoprotein immunodeficiency-virus type-1 t alternative exon site selection exponential enrichment systematic evolution regulatory elements distinct functions premessenger rna
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 > genetics & nucleic acid processing > DNA, RNA structure, function, modification > exons > exon splicing
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > pre-mRNA
CSHL Authors:
Communities: CSHL labs > Krainer lab
CSHL labs > Zhang lab
Depositing User: Matt Covey
Date: July 1998
Date Deposited: 11 Dec 2013 15:32
Last Modified: 11 Dec 2013 15:32
PMCID: PMC316967
Related URLs:
URI: http://repository.cshl.edu/id/eprint/28934

Actions (login required)

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