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Nat Commun. 2019 Aug 9;10(1):3629. doi: 10.1038/s41467-019-11585-z.

A conserved RNA structural motif for organizing topology within picornaviral internal ribosome entry sites.

Author information

1
Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL, 60637, USA.
2
Department of Biochemistry, Stanford University School of Medicine, Stanford, CA, 94305, USA.
3
Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL, 60637, USA. jpicciri@uchicago.edu.
4
Department of Chemistry, The University of Chicago, Chicago, IL, 60637, USA. jpicciri@uchicago.edu.

Abstract

Picornaviral IRES elements are essential for initiating the cap-independent viral translation. However, three-dimensional structures of these elements remain elusive. Here, we report a 2.84-Å resolution crystal structure of hepatitis A virus IRES domain V (dV) in complex with a synthetic antibody fragment-a crystallization chaperone. The RNA adopts a three-way junction structure, topologically organized by an adenine-rich stem-loop motif. Despite no obvious sequence homology, the dV architecture shows a striking similarity to a circularly permuted form of encephalomyocarditis virus J-K domain, suggesting a conserved strategy for organizing the domain architecture. Recurrence of the motif led us to use homology modeling tools to compute a 3-dimensional structure of the corresponding domain of foot-and-mouth disease virus, revealing an analogous domain organizing motif. The topological conservation observed among these IRESs and other viral domains implicates a structured three-way junction as an architectural scaffold to pre-organize helical domains for recruiting the translation initiation machinery.

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