Poliovirus 2A protease triggers a selective nucleo-cytoplasmic redistribution of splicing factors to regulate alternative pre-mRNA splicing.
Poliovirus protease 2A (2A(pro)) obstructs host gene expression by reprogramming transcriptional and post-transcriptional regulatory events during infection. Here we demonstrate that expression of 2A(pro) induces a selective nucleo-cytoplasm translocation of several important RNA binding proteins and splicing factors. Subcellular fractionation studies, together with immunofluorescence microscopy revealed an asymmetric distribution of HuR and TIA1/TIAR in 2A(pro) expressing cells, which modulates splicing of the human Fas exon 6. Consistent with this result, knockdown of HuR or overexpression of TIA1/TIAR, leads to Fas exon 6 inclusion in 2A(pro)-expressing cells. Therefore, poliovirus 2A(pro) can target alternative pre-mRNA splicing by regulating protein shuttling between the nucleus and the cytoplasm.
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid (CSIC-UAM), Madrid, Spain.
Enrique
E
Álvarez
Alfredo
A
Castelló
Luis
L
Carrasco
José M
JM
Izquierdo
D017398:Alternative Splicing / Q000235:genetics / Q000502:physiology*; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D005091:Exons / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D017955:Poliovirus / Q000201:enzymology*; D012322:RNA Precursors / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics / Q000502:physiology*
D012322:RNA Precursors