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Updated: Jun 5, 2026

Advancing High-Resolution Imaging of Virus Assemblies in Liquid and Ice
Published on: July 20, 2022
Crystal structures of complexes containing domains from two viral internal ribosome entry site (IRES) RNAs bound to
Jianyu Zhu1, Andrei Korostelev, David A Costantino
1Center for Molecular Biology of RNA and Department of Molecular, Cell and Developmental Biology, Sinsheimer Labs, University of California, Santa Cruz, CA 95064, USA.
Abstract:
Internal ribosome entry site (IRES) RNAs are elements of viral or cellular mRNAs that bypass steps of canonical eukaryotic cap-dependent translation initiation. Understanding of the structural basis of IRES mechanisms is limited, partially due to a lack of high-resolution structures of IRES RNAs bound to their cellular targets. Prompted by the universal phylogenetic conservation of the ribosomal P site, we solved the crystal structures of proposed P site binding domains from two intergenic region IRES RNAs bound to bacterial 70S ribosomes. The structures show that these IRES domains nearly perfectly mimic a tRNA • mRNA interaction. However, there are clear differences in the global shape and position of this IRES domain in the intersubunit space compared to those of tRNA, supporting a mechanism for IRES action that invokes hybrid state mimicry to drive a noncanonical mode of translocation. These structures suggest how relatively small structured RNAs can manipulate complex biological machines.
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