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Title: Alternative splicing, a new target to block cellular gene expression by poliovirus 2A protease

Abstract

Highlights: {yields} Novel role for poliovirus 2A protease as splicing modulator. {yields} Poliovirus 2A protease inhibits the alternative splicing of pre-mRNAs. {yields} Poliovirus 2A protease blocks the second catalytic step of splicing. -- 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{sup pro} modulating the alternative splicing of pre-mRNAs. Expression of 2A{sup pro} potently inhibits splicing of reporter genes in HeLa cells. Low amounts of 2A{sup 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{sup 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{sup pro} on splicing is to selectively block the second catalytic step.

Authors:
 [1]; ; ;  [1]
  1. Centro de Biologia Molecular Severo Ochoa (CSIC-UAM), Nicolas Cabrera, 1 Universidad Autonoma de Madrid, Cantoblanco, 28049 Madrid (Spain)
Publication Date:
OSTI Identifier:
22207521
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 414; Journal Issue: 1; Other Information: Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; GENES; HELA CELLS; IN VITRO; MESSENGER-RNA; POLIO VIRUS; SPLICING

Citation Formats

Alvarez, Enrique, Castello, Alfredo, Carrasco, Luis, and Izquierdo, Jose M. Alternative splicing, a new target to block cellular gene expression by poliovirus 2A protease. United States: N. p., 2011. Web. doi:10.1016/J.BBRC.2011.09.040.
Alvarez, Enrique, Castello, Alfredo, Carrasco, Luis, & Izquierdo, Jose M. Alternative splicing, a new target to block cellular gene expression by poliovirus 2A protease. United States. https://doi.org/10.1016/J.BBRC.2011.09.040
Alvarez, Enrique, Castello, Alfredo, Carrasco, Luis, and Izquierdo, Jose M. 2011. "Alternative splicing, a new target to block cellular gene expression by poliovirus 2A protease". United States. https://doi.org/10.1016/J.BBRC.2011.09.040.
@article{osti_22207521,
title = {Alternative splicing, a new target to block cellular gene expression by poliovirus 2A protease},
author = {Alvarez, Enrique and Castello, Alfredo and Carrasco, Luis and Izquierdo, Jose M.},
abstractNote = {Highlights: {yields} Novel role for poliovirus 2A protease as splicing modulator. {yields} Poliovirus 2A protease inhibits the alternative splicing of pre-mRNAs. {yields} Poliovirus 2A protease blocks the second catalytic step of splicing. -- 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{sup pro} modulating the alternative splicing of pre-mRNAs. Expression of 2A{sup pro} potently inhibits splicing of reporter genes in HeLa cells. Low amounts of 2A{sup 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{sup 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{sup pro} on splicing is to selectively block the second catalytic step.},
doi = {10.1016/J.BBRC.2011.09.040},
url = {https://www.osti.gov/biblio/22207521}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 1,
volume = 414,
place = {United States},
year = {Fri Oct 14 00:00:00 EDT 2011},
month = {Fri Oct 14 00:00:00 EDT 2011}
}