The adenovirus E4-ORF4 splicing enhancer protein interacts with a subset of phosphorylated SR proteins

Nilsson, C. E., Petersen-Mahrt, S., Durot, C., Shtrichman, R., Krainer, A. R., Kleinberger, T., Akusjarvi, G. (February 2001) The adenovirus E4-ORF4 splicing enhancer protein interacts with a subset of phosphorylated SR proteins. EMBO Journal, 20 (4). pp. 864-871. ISSN 0261-4189

URL: http://www.ncbi.nlm.nih.gov/pubmed/11179230
DOI: 10.1093/emboj/20.4.864

Abstract

SR proteins purified from uninfected HeLa cells inhibit adenovirus IIIa pre-mRNA splicing by binding to the intronic ma repressor element (3RE), In contrast, SR proteins purified from late adenovirus-infected cells are functionally inactivated as splicing repressor proteins by a virus-induced dephosphorylation, We have shown that the adenovirus E4-ORF4 protein, which binds the cellular protein phosphatase 2A (PP2A) and activates IIIa splicing in vitro and lit vivo, induces SR protein dephosphorylation, Here we show that E4-ORF4 interacts with only a subset of SR proteins present in HeLa cells. Thus, E4-ORF4 interacts efficiently with SF2/ASF and SRp30c, but not with other SR proteins. Interestingly, E4-ORF4 interacts with SF2/ASF through the latter's RNA recognition motifs, Furthermore, E4-ORF4 interacts preferentially with the hyperphosphorylated form of SR proteins found in uninfected HeLa cells. E4-ORF4 mutant proteins that fail to bind strongly to PP2A or SF2/ASF do not relieve the repressive effect of HeLa SR proteins on IIIa pre-mRNA splicing in transient transfection experiments, suggesting that an interaction between all three proteins is required for E4-ORF4-induced SR protein dephosphorylation.

Item Type: Paper
Uncontrolled Keywords: adenovirus E4-ORF protein protein phosphatase 2A splicing enhancer SR proteins pre-messenger-rna e4orf4 protein phosphatase 2a p53-independent apoptosis transformed-cells b-alpha transcription expression domains asf/sf2
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
organism description > virus > adenovirus
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > pre-mRNA
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > protein phosphatase
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > RNA splicing
CSHL Authors:
Communities: CSHL labs > Krainer lab
Depositing User: Matt Covey
Date: February 2001
Date Deposited: 11 Dec 2013 19:33
Last Modified: 11 Dec 2013 19:33
PMCID: PMC145406
Related URLs:
URI: http://repository.cshl.edu/id/eprint/28907

Actions (login required)

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