title: Alternative splicing, a new target to block cellular gene expression by poliovirus 2A protease.
abstract: Viruses have developed multiple strategies to interfere with the gene expression of host cells at different stages to ensure their own survival. Here we report a new role for poliovirus 2A(pro) modulating the alternative splicing of pre-mRNAs. Expression of 2A(pro) potently inhibits splicing of reporter genes in HeLa cells. Low amounts of 2A(pro) abrogate Fas exon 6 skipping, whereas higher levels of protease fully abolish Fas and FGFR2 splicing. In vitro splicing of MINX mRNA using nuclear extracts is also strongly inhibited by 2A(pro), leading to accumulation of the first exon and the lariat product containing the unspliced second exon. These findings reveal that the mechanism of action of 2A(pro) on splicing is to selectively block the second catalytic step.
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Nicolás Cabrera, 1 Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain. ealvarez@cbm.uam.es
authors.forename: Enrique
authors.initials: E
authors.lastname: Álvarez
authors.forename: Alfredo
authors.initials: A
authors.lastname: Castelló
authors.forename: Luis
authors.initials: L
authors.lastname: Carrasco
authors.forename: José M
authors.initials: JM
authors.lastname: Izquierdo
mesh_terms: D017398:Alternative Splicing; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D005091:Exons; D015870:Gene Expression; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D011051:Poliomyelitis / Q000235:genetics; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D019014:fas Receptor / Q000235:genetics
chemical_list: D014764:Viral Proteins; D019014:fas Receptor; C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2; D003546:Cysteine Endopeptidases; C057400:picornain 2A, Picornavirus