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

Estmer Nilsson, CamillaUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi (author)

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

Petersen-Mahrt, SvendUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi (author)
Durot, C (author)
Shtrichman, R (author)
Krainer, AR (author)
Kleinberger, T (author)
Akusjärvi, GöranUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi(Swepub:uu)gak30132 (author)
Uppsala universitetInstitutionen för medicinsk biokemi och mikrobiologi (creator_code:org_t)

By the author/editor: Estmer Nilsson, ...; Petersen-Mahrt, ...; Durot, C; Shtrichman, R; Krainer, AR; Kleinberger, T; show more...; Akusjärvi, Göran; show less...

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