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
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.
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