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Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Picornavirus IRES: Structure Function Relationship

Author(s): Encarnacion Martinez-Salas and Olga Fernandez-Miragall

Volume 10, Issue 30, 2004

Page: [3757 - 3767] Pages: 11

DOI: 10.2174/1381612043382657

Price: $65

Abstract

Picornavirus infections have been a challenging problem in human health. Genome organisation of picornavirus is unique in having a long, heavily-structured, multifunctional 5untranslated region, preceding a single open reading frame from which all viral proteins are produced. Within the 5leader, an internal region termed ribosome entry site (IRES) regulates viral protein synthesis in a 5-independent manner. The IRES element itself is a distinctive feature of the picornavirus mRNAs, allowing efficient viral protein synthesis in infected cells in spite of a severe modification of translation initiation factors induced by viral proteases that lead to a fast inhibition of cellular protein synthesis. Picornavirus IRES elements are strongly structured, bearing several motifs, phylogenetically conserved, which are essential for IRES activity. Together with RNA structure, RNA-binding proteins play an essential role in the activity of the IRES element, having a profound effect on viral pathogenesis. Recent data on the involvement of these conserved motifs in RNA structure and protein recognition is discuss ed in detail. Understanding the interplay between these two components of IRES function is crucial to develop viral strategies aimed to use the viral RNA as the target of antiviral approaches.

Keywords: picornavirus, internal ribosome entry site, protein synthesis, translation initiation factors, rna-binding proteins, rna structure, rna target


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