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The adenovirus E4-ORF4 splicing enhancer protein interacts with a subsetof phosphorylated SR proteins
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
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2001 (English)In: EMBO Journal, ISSN 0261-4189, E-ISSN 1460-2075, Vol. 20, 864-871 p.Article in journal (Refereed) Published
Abstract [en]

SR proteins purified from uninfected HeLa cells inhibit adenovirus IIIa pre-mRNA splicing by binding to the intronic IIIa 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 phos phatase 2A (PP2A) and activates IIIa splicing in vitro and in 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

Place, publisher, year, edition, pages
2001. Vol. 20, 864-871 p.
Keyword [en]
adenovirus, E4-ORF protein, protein phosphatase 2A, splicing enhancer, SR proteins
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-52465DOI: 10.1093/emboj/20.4.86410.1093/emboj/20.4.864PubMedID: 11179230OAI: oai:DiVA.org:uu-52465DiVA: diva2:80374
Available from: 2008-10-17 Created: 2008-10-17 Last updated: 2017-12-04Bibliographically approved

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Akusjärvi, Göran

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