Poliovirus 2A Protease Triggers a Selective Nucleo-Cytoplasmic Redistribution of Splicing Factors to Regulate Alternative Pre-mRNA Splicing

被引:30
作者
Alvarez, Enrique [1 ]
Castello, Alfredo [2 ]
Carrasco, Luis [1 ]
Izquierdo, Jose M. [1 ]
机构
[1] Univ Autonoma Madrid, CSIC, Ctr Biol Mol Severo Ochoa, Madrid, Spain
[2] European Mol Biol Lab, D-69012 Heidelberg, Germany
关键词
PORE COMPLEX PROTEINS; TIA-1; VIRUSES;
D O I
10.1371/journal.pone.0073723
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页数:7
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