Poliovirus 2A protease triggers a selective nucleo-cytoplasmic redistribution of splicing factors to regulate alternative pre-mRNA splicing

Álvarez, E., Castelló, A. , Carrasco, L. and Izquierdo, J. M. (2013) Poliovirus 2A protease triggers a selective nucleo-cytoplasmic redistribution of splicing factors to regulate alternative pre-mRNA splicing. PLoS ONE, 8(9), e73723. (doi: 10.1371/journal.pone.0073723) (PMID:24066065) (PMCID:PMC3774746)

Abstract

Poliovirus protease 2A (2Apro) obstructs host gene expression by reprogramming transcriptional and post-transcriptional regulatory events during infection. Here we demonstrate that expression of 2Apro 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 2Apro 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 2Apro-expressing cells. Therefore, poliovirus 2Apro can target alternative pre-mRNA splicing by regulating protein shuttling between the nucleus and the cytoplasm.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Castello, Professor Alfredo
• Authors: Álvarez, E., Castelló, A., Carrasco, L., and Izquierdo, J. M.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: PLoS ONE
• Publisher: Public Library of Science
• ISSN: 1932-6203
• ISSN (Online): 1932-6203
• Copyright Holders: Copyright © 2013 Álvarez et al.
• First Published: First published in PLoS ONE 8(9): e73723
• Publisher Policy: Reproduced under a Creative Commons License