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Nucleic Acids Res. 2013 Feb 1;41(3):1483-95. doi: 10.1093/nar/gks1302. Epub 2012 Dec 28.

Candidate RNA structures for domain 3 of the foot-and-mouth-disease virus internal ribosome entry site.

Author information

1
Department of Chemistry, Courant Institute of Mathematical Sciences, New York University, 251 Mercer Street, New York, NY 10012, USA.

Abstract

The foot-and-mouth-disease virus (FMDV) utilizes non-canonical translation initiation for viral protein synthesis, by forming a specific RNA structure called internal ribosome entry site (IRES). Domain 3 in FMDV IRES is phylogenetically conserved and highly structured; it contains four-way junctions where intramolecular RNA-RNA interactions serve as a scaffold for the RNA to fold for efficient IRES activity. Although the 3D structure of domain 3 is crucial to exploring and deciphering the initiation mechanism of translation, little is known. Here, we employ a combination of various modeling approaches to propose candidate tertiary structures for the apical region of domain 3, thought to be crucial for IRES function. We begin by modeling junction topology candidates and build atomic 3D models consistent with available experimental data. We then investigate each of the four candidate 3D structures by molecular dynamics simulations to determine the most energetically favorable configurations and to analyze specific tertiary interactions. Only one model emerges as viable containing not only the specific binding site for the GNRA tetraloop but also helical arrangements which enhance the stability of domain 3. These collective findings, together with available experimental data, suggest a plausible theoretical tertiary structure of the apical region in FMDV IRES domain 3.

PMID:
23275533
PMCID:
PMC3561949
DOI:
10.1093/nar/gks1302
[Indexed for MEDLINE]
Free PMC Article

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