tRNA–mRNA mimicry drives translation initiation from a viral IRES. Translation initiation at the CUU codon is mediated by the internal ribosome entry site of an insect picorna-like virus in vitro. Methionine-independent initiation of translation in the capsid protein of an insect RNA virus. Initiation of protein synthesis from the A site of the ribosome. Internal initiation in Saccharomyces cerevisiae mediated by an initiator tRNA/eIF2-independent internal ribosome entry site element.

Initiator Met-tRNA-independent translation mediated by an internal ribosome entry site element in cricket paralysis virus-like insect viruses. Structural elements in the internal ribosome entry site of Plautia stali intestine virus responsible for binding with ribosomes. Factorless ribosome assembly on the internal ribosome entry site of cricket paralysis virus. Position of the CrPV IRES on the 40S subunit and factor dependence of IRES/80S ribosome assembly. Cryo-EM visualization of a viral internal ribosome entry site bound to human ribosomes: the IRES functions as an RNA-based translation factor. Structure of the ribosome-bound cricket paralysis virus IRES RNA. Mechanism of translation initiation by Dicistroviridae IGR IRESs. Interchangeability of factors and tRNA’s in bacterial and eukaryotic translation initiation systems. Leaderless mRNAs in bacteria: surprises in ribosomal recruitment and translational control. Translation initiation: variations in the mechanism can be anticipated. One core, two shells: bacterial and eukaryotic ribosomes. Principles of translational control: an overview.

This IRES RNA bridges billions of years of evolutionary divergence and provides an example of an RNA structure-based translation initiation signal capable of operating in two domains of life. Initiation in both bacteria and eukaryotes depends on the structure of the IRES RNA, but in bacteria this RNA uses a different mechanism that includes a form of ribosome repositioning after initial recruitment. We solved the crystal structure of this IRES bound to a bacterial ribosome to 3.8 Å resolution, revealing that despite differences between bacterial and eukaryotic ribosomes this IRES binds directly to both and occupies the space normally used by transfer RNAs. Here we report our discovery that a eukaryotic viral IRES can initiate translation in live bacteria.

Although structured internal ribosome entry site (IRES) RNAs can manipulate ribosomes to initiate translation in eukaryotic cells, an analogous RNA structure-based mechanism has not been observed in bacteria. We wanted to explore whether an undiscovered RNA-based signal might be able to use these conserved features, bypassing mechanisms specific to each domain of life, and initiate protein synthesis in both bacteria and eukaryotes. However, the core structures and conformational dynamics of ribosomes that are responsible for the translation steps that take place after initiation are ancient and conserved across the domains of life 2. For example, the canonical molecular signals used to initiate protein synthesis in bacteria and eukaryotes are mutually exclusive 1. The central dogma of gene expression (DNA to RNA to protein) is universal, but in different domains of life there are fundamental mechanistic differences within this pathway.

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