Nucleic Acids Research Advance Access originally published online on August 28, 2007
Nucleic Acids Research 2007 35(17):5975-5984; doi:10.1093/nar/gkm645
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Nucleic Acids Research, 2007, Vol. 35, No. 17 5975-5984
© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
RNA |
Poly(A) binding protein, C-terminally truncated by the hepatitis A virus proteinase 3C, inhibits viral translation
1Institute of Medical Molecular Biology, University of Lübeck, Germany and 2Istituto Superiore di Sanita, Rome, Italy
*To whom correspondence should be addressed. Tel: +49 451 500 4085; Fax: +49 451 500 3637; Email: gaussmue{at}molbio.uni-luebeck.de
Received July 6, 2007. Revised August 2, 2007. Accepted August 3, 2007.
Proteolytic cleavage of translation initiation factors is a means to interfere with mRNA circularization and to induce translation arrest during picornaviral replication or apoptosis. It was shown that the regulated cleavages of eukaryotic initiation factor (eIF) 4G and poly(A)-binding protein (PABP) by viral proteinases correlated with early and late arrest of host cap-dependent and viral internal ribosome entry site (IRES)-dependent translation, respectively. Here we show that in contrast to coxsackievirus, eIF4G is not a substrate of proteinase 3C of hepatitis A virus (HAV 3Cpro). However, PABP is cleaved by HAV 3Cpro in vitro and in vivo, separating the N-terminal RNA-binding domain (NTD) of PABP from the C-terminal protein-interaction domain. In vitro, NTD has a dominant negative effect on HAV IRES-dependent translation and an enhanced binding affinity to the RNA structural element pY1 in the 5' nontranslated region of the HAV RNA that is essential for viral genome replication. The results point to a regulatory role of PABP cleavage in RNA template switching of viral translation to RNA synthesis.
Present address: Bo Zhang, DAI 4085, Wadsworth Center, New York State Department of Health, 120 New Scotland Ave, Albany, New York, 12208, USA.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. M. Bonderoff, J. L. LaRey, and R. E. Lloyd Cleavage of Poly(A)-Binding Protein by Poliovirus 3C Proteinase Inhibits Viral Internal Ribosome Entry Site-Mediated Translation J. Virol., October 1, 2008; 82(19): 9389 - 9399. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. Dufresne, E. Ubalijoro, M. G. Fortin, and J.-F. Laliberte Arabidopsis thaliana class II poly(A)-binding proteins are required for efficient multiplication of turnip mosaic virus J. Gen. Virol., September 1, 2008; 89(9): 2339 - 2348. [Abstract] [Full Text] [PDF]
|
|