Taura syndrome virus IRES initiates translation by binding its tRNA-mRNA–like structural element in the ribosomal decoding center

Koh, Cha San; Brilot, Axel F.; Grigorieff, Nikolaus; Коростелев, А.A.

doi:10.1073/pnas.1406335111

Cited by 58 publications

(125 citation statements)

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“…Cycloheximide inhibits translation by binding to the ribosomal E site, and as such, these observations are consistent with a model in which the IRES initially occupies the P site to direct translation from the A site (18,32). In light of the recent highresolution structural data presenting evidence that initial ribosome binding positions the PKI domain of the IRES in the ribosomal A site, we reevaluated the initial translocation steps of ribosomes assembled on the IRES (20,22).…”

Section: A6554 and A6576 Contribute To Ires-mediated Translation Andsupporting

confidence: 73%

“…3A, lanes 1 and 2). This toeprint represents a ribosome positioned at the IRES translational start site with the PKI domain in the ribosomal A site (20,22,23). The +14 A6628 toeprint was not observed for an IRES mutant deficient in ribosome positioning (ΔPKI) (Fig.…”

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confidence: 99%

“…The functions of these extra features are not well understood. Although initial biochemical data and low-resolution cryo-EM reconstructions suggested an early model in which the IGR IRES PKI domain occupies the E, P, and partially the A sites to direct translation at the non-AUG codon in the A site (6,14,(17)(18)(19), recent high-resolution cryo-EM structures of IRES-ribosome complexes reveal that the PKI domain occupies the A site on initial binding to the ribosome (20)(21)(22)(23). Subsequent translocation into the P site by elongation factor 2 is a prerequisite for presenting the non-AUG initiation codon of the IRES to the incoming aminoacyl-tRNA in the A site.…”

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confidence: 99%

“…Indeed, with chimeric IRESs, the ribosome-binding and PKI domains of type I and II IRESs are functionally interchangeable (30,31). Recent cryo-EM structures of the Taura syndrome virus (TSV) type II IRES bound to the ribosome confirmed that similar interactions with the ribosome are shared between type I and II IRESs (22). Interestingly, the TSV SLIII, which is stacked coaxially on PKI, extends toward the A site of the large ribosomal subunit (22).…”

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confidence: 99%

“…Recent cryo-EM structures of the Taura syndrome virus (TSV) type II IRES bound to the ribosome confirmed that similar interactions with the ribosome are shared between type I and II IRESs (22). Interestingly, the TSV SLIII, which is stacked coaxially on PKI, extends toward the A site of the large ribosomal subunit (22). Disruption of SLIII base pairing inhibits TSV IRES translation, which can be effectively restored by compensatory mutations (29).…”

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confidence: 99%

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Global shape mimicry of tRNA within a viral internal ribosome entry site mediates translational reading frame selection

Cornilescu

Mouzakis

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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The dicistrovirus intergenic region internal ribosome entry site (IRES) adopts a triple-pseudoknotted RNA structure and occupies the core ribosomal E, P, and A sites to directly recruit the ribosome and initiate translation at a non-AUG codon. A subset of dicistrovirus IRESs directs translation in the 0 and +1 frames to produce the viral structural proteins and a +1 overlapping open reading frame called ORFx, respectively. Here we show that specific mutations of two unpaired adenosines located at the core of the threehelical junction of the honey bee dicistrovirus Israeli acute paralysis virus (IAPV) IRES PKI domain can uncouple 0 and +1 frame translation, suggesting that the structure adopts distinct conformations that contribute to 0 or +1 frame translation. Using a reconstituted translation system, we show that ribosomes assembled on mutant IRESs that direct exclusive 0 or +1 frame translation lack reading frame fidelity. Finally, a nuclear magnetic resonance/small-angle X-ray scattering hybrid approach reveals that the PKI domain of the IAPV IRES adopts an RNA structure that resembles a complete tRNA. The tRNA shape-mimicry enables the viral IRES to gain access to the ribosome tRNA-binding sites and form intermolecular contacts with the ribosome that are necessary for initiating IRES translation in a specific reading frame.translation | virus | RNA | ribosome | internal ribosome entry site F idelity of protein synthesis and the transmission of genetic information from mRNA into a nascent protein rely on the accurate selection and maintenance of the translational reading frame. In canonical eukaryotic translation, after recruitment and scanning of ribosomes on an mRNA, the translational reading frame is initially established by methionyl-tRNA i anticodon: codon pairing in the ribosomal P site. Although the mechanisms that specify reading frame selection and maintenance during translation are not completely understood, programmed recoding mechanisms that have been identified in some viral and cellular mRNAs have yielded significant insights into the cis-acting signals that increase coding capacity or allow translation using alternate reading frames (1, 2).We recently demonstrated that a subset of viruses within the Dicistroviridae family harbors an intergenic region internal ribosome entry site (IGR IRES) that can direct translation in alternative reading frames (3), providing an excellent model for studying RNA-ribosome interactions that influence reading frame selection. An IRES is generally a structured RNA element that can recruit the ribosome in a 5′ end-independent manner and without the full complement of canonical translation initiation factors (4, 5). Among the diverse types of IRES elements found in both viral and messenger RNAs, the IGR IRES uses the most streamlined mechanism, dispensing the need for all canonical initiation factors to directly recruit the ribosome and initiate translation at a non-AUG codon (6-8). The IGR IRES adopts an RNA structure comprising two independently folded domains; ps...

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Section: A6554 and A6576 Contribute To Ires-mediated Translation Andsupporting

confidence: 73%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Global shape mimicry of tRNA within a viral internal ribosome entry site mediates translational reading frame selection

Cornilescu

Mouzakis

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Protein Synthesis Initiation in Eukaryotes: IRES ‐mediated Internal Initiation

Svitkin

Siddiqui

Sonenberg

2015

Encyclopedia of Life Sciences

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The major mechanism of translation initiation in eukaryotes involves recognition of the cap structure at the 5′ end of the mRNA by the cap‐binding protein eIF4E. Internal ribosome entry sites (IRES) are specialised RNA sequences that are capable of recruiting ribosomes to an internal position of an mRNA in a cap‐independent manner. Many viruses have evolved this alternative pathway to initiate translation. Viral IRESs bind ribosomes by several mechanisms that require different sets of canonical initiation factors. In addition, IRES activity is modulated by IRES trans‐acting factors (ITAFs). Some cellular mRNAs are suggested to contain IRESs, as they function in cells under stress and other conditions when cap‐dependent initiation is inhibited. However, solid evidence for internal ribosome entry onto many of these mRNAs is lacking. Key Concepts In eukaryotes, the majority of mRNAs are translated by a 5′ end‐dependent mechanism, in which the mRNA 5′ cap structure recruits the translation machinery. Specific RNA elements, termed internal ribosome entry sites (IRESs), can direct ribosomes to internal positions of mRNAs to initiate translation. IRESs in viral RNA genomes differ significantly with respect to their structure and initiation factor requirements. In addition to some canonical initiation factors, IRES‐mediated translation may require ITAFs (IRES trans ‐acting factors). Many cellular mRNAs are suggested to possess IRESs, as they remain active under a number of pathophysiological stress conditions when cap‐dependent translation is inhibited. The authenticity of some cellular IRESs remains controversial as being not confirmed in recently developed stringent tests for IRES activity.

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Viral internal ribosomal entry sites: four classes for one goal

2017

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To ensure efficient propagation, viruses need to rapidly produce viral proteins after cell entrance. Since viral genomes do not encode any components of the protein biosynthesis machinery, viral proteins must be produced by the host cell. To hi-jack the host cellular translation, viruses use a great variety of distinct strategies. Many single-stranded positive-sensed RNA viruses contain so-called internal ribosome entry sites (IRESs). IRESs are structural RNA motifs that have evolved to specific folds that recruit the host ribosomes on the viral coding sequences in order to synthesize viral proteins. In host canonical translation, recruitment of the translation machinery components is essentially guided by the 5' cap (m G) of mRNA. In contrast, IRESs are able to promote efficient ribosome assembly internally and in cap-independent manner. IRESs have been categorized into four classes, based on their length, nucleotide sequence, secondary and tertiary structures, as well as their mode of action. Classes I and II require the assistance of cellular auxiliary factors, the eukaryotic intiation factors (eIF), for efficient ribosome assembly. Class III IRESs require only a subset of eIFs whereas Class IV, which are the more compact, can promote translation without any eIFs. Extensive functional and structural investigations of IRESs over the past decades have allowed a better understanding of their mode of action for viral translation. Because viral translation has a pivotal role in the infectious program, IRESs are therefore attractive targets for therapeutic purposes. WIREs RNA 2018, 9:e1458. doi: 10.1002/wrna.1458 This article is categorized under: Translation > Ribosome Structure/Function Translation > Translation Mechanisms RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes.

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Taura syndrome virus IRES initiates translation by binding its tRNA-mRNA–like structural element in the ribosomal decoding center

Cited by 58 publications

References 62 publications

Global shape mimicry of tRNA within a viral internal ribosome entry site mediates translational reading frame selection

Global shape mimicry of tRNA within a viral internal ribosome entry site mediates translational reading frame selection

Protein Synthesis Initiation in Eukaryotes: IRES ‐mediated Internal Initiation

Viral internal ribosomal entry sites: four classes for one goal

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