The adenovirus E4-ORF4 splicing enhancer protein interacts with a subsetof phosphorylated SR proteins
2001 (English)In: EMBO Journal, ISSN 0261-4189, E-ISSN 1460-2075, Vol. 20, 864-871 p.Article in journal (Refereed) Published
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.
adenovirus, E4-ORF protein, protein phosphatase 2A, splicing enhancer, SR proteins
Medical and Health Sciences
IdentifiersURN: 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