Two Alternative Ways of Start Site Selection in Human Norovirus Reinitiation of Translation

Luttermann, Christine; Meyers, Gregor

doi:10.1074/jbc.m114.554030

Cited by 16 publications

(37 citation statements)

References 54 publications

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“…CUA or UCG) reduced reinitiation by only 3–4 fold (Meyers, 2003; Lütterman and Meyers, 2007, 2014; Napthine et al, 2009). To determine the basis for this plasticity, we investigated reinitiation by post-termination 80S ribosomes and by recycled 40S subunits on mutant RHDV mRNAs, in which the restart AUG was replaced by near-cognate UUG and ACG codons, or by a non-cognate CUU codon.…”

Section: Resultsmentioning

confidence: 99%

“…Reinitiation on calicivirus mRNAs does not have a strict requirement for maintenance of the wt spacing between stop and restart codons (Meyers, 2003; Meyers, 2007; Lütterman and Meyers, 2007, 2014). To evaluate the preference for the position of the restart AUG, we therefore moved the stop codon 9nt downstream together with the six upstream nucleotides of its native context, thus creating an additional AUG (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The best-characterized example is reinitiation on positive strand RNA viruses of the family Caliciviridae , such as rabbit hemorrhagic disease virus (RHDV) (Meyers 2003, 2007), feline calicivirus (FCV) (Lütterman and Meyers 2007, 2009; Pöyry et al, 2007) and bovine, human and murine noroviruses (NV) (Lütterman and Meyers, 2014; McCormick et al, 2008; Naphthine et al, 2009). In bicistronic subgenomic (sg) calicivirus mRNAs encoding major and minor capsid proteins, translation of the second cistron occurs by reinitiation.…”

Section: Introductionmentioning

confidence: 99%

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Multiple Mechanisms of Reinitiation on Bicistronic Calicivirus mRNAs

2015

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Reinitiation is a strategy used by viruses to express several cistrons from one mRNA. Although extremely weak after translation of long ORFs on cellular mRNAs, reinitiation occurs efficiently on subgenomic bicistronic calicivirus mRNAs, enabling synthesis of minor capsid proteins. The process is governed by a short element upstream of the restart AUG designated “termination upstream ribosomal binding site” (TURBS). It contains the conserved Motif 1 complementary to h26 of 18S rRNA, displayed in the loop of a hairpin formed by species-specific Motifs 2/2*. To determine the advantages conferred on reinitiation by TURBS, we reconstituted this process in vitro on two model bicistronic calicivirus mRNAs. We found that post-termination ribosomal tethering of mRNA by TURBS allows reinitiation by post-termination 80S ribosomes, and diminishes dependence on eIF3 of reinitiation by recycled 40S subunits, which can be mediated either by eIFs 2/1/1A or by Ligatin following ABCE1-dependent or -independent splitting of post-termination complexes.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Multiple Mechanisms of Reinitiation on Bicistronic Calicivirus mRNAs

2015

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“…That the predicted pseudoknot must be located closely upstream of the CP stop codon (Li et al, 2011) suggests a functional role for this structure in tethering the terminating ribosome or components thereof, which can then reinitiate with limited efficiency at a nearby start codon. These findings and suggested mechanism for victoriviruses are reminiscent of translational reinitiation as characterized to date in influenza B viruses and caliciviruses, which contain a required RNA region termed the TURBS within 90 nt upstream of the stop/restart codons (Horvath et al, 1990;Luttermann and Meyers, 2007, 2014McCormick et al, 2008;Meyers, 2003Meyers, , 2007Napthine et al, 2009;Powell et al, 2008Powell et al, , 2011Pöyry et al, 2007). The TURBS functions in part via a short sequence within it that base-pairs with host 18S rRNA and thereby helps to retain the 40S ribosome after translational termination on the upstream ORF.…”

Section: Discussionmentioning

confidence: 84%

“…In influenza B viruses and caliciviruses, a stretch of r90 nucleotides (nt) in the upstream ORF, termed the "termination upstream ribosome binding site" (TURBS) and located directly upstream of the downstream ORF's start codon, is required for reinitiation (Horvath et al, 1990;Luttermann and Meyers, 2007, 2014McCormick et al, 2008;Meyers, 2003Meyers, , 2007Napthine et al, 2009;Powell et al, 2008Powell et al, , 2011Pöyry et al, 2007). Moreover, within the TURBS of each of these viruses, one or more stem-loop structures appear to be required, as well as a short stretch of primary sequences that base-pair with host 18S rRNA and thereby contribute to tethering the 40S subunit.…”

Section: Introductionmentioning

confidence: 99%

An RNA cassette from Helminthosporium victoriae virus 190S necessary and sufficient for stop/restart translation

Havens

Nibert

et al. 2015

Virology

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Prototype victorivirus HvV190S employs stop/restart translation to express its RdRp from the downstream ORF in its bicistronic mRNA. The signals for this activity appear to include a predicted RNA pseudoknot directly upstream of the CP stop and RdRp start codons, which overlap in the motif AUGA. Here we used a dual-fluorescence system to further define which HvV190S sequences are important for stop/restart translation and found that the AUGA motif plus 38 nt directly upstream are both necessary and sufficient for this activity. This RNA cassette encompasses the predicted pseudoknot, and indeed substitutions that disrupted the pseudoknot disrupted the activity whereas complementary substitutions that restored the pseudoknot restored the activity. Replacement of this RNA cassette with those from other victoriviruses with a predicted pseudoknot in comparable position also supported stop/restart translation. To our knowledge, this is the first example of stop/restart translation regulated by an RNA pseudoknot.

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Translation initiation by cap‐dependent ribosome recruitment: Recent insights and open questions

2018

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Gene expression universally relies on protein synthesis, where ribosomes recognize and decode the messenger RNA template by cycling through translation initiation, elongation, and termination phases. All aspects of translation have been studied for decades using the tools of biochemistry and molecular biology available at the time. Here, we focus on the mechanism of translation initiation in eukaryotes, which is remarkably more complex than prokaryotic initiation and is the target of multiple types of regulatory intervention. The "consensus" model, featuring cap-dependent ribosome entry and scanning of mRNA leader sequences, represents the predominantly utilized initiation pathway across eukaryotes, although several variations of the model and alternative initiation mechanisms are also known. Recent advances in structural biology techniques have enabled remarkable molecular-level insights into the functional states of eukaryotic ribosomes, including a range of ribosomal complexes with different combinations of translation initiation factors that are thought to represent bona fide intermediates of the initiation process. Similarly, high-throughput sequencing-based ribosome profiling or "footprinting" approaches have allowed much progress in understanding the elongation phase of translation, and variants of them are beginning to reveal the remaining mysteries of initiation, as well as aspects of translation termination and ribosomal recycling. A current view on the eukaryotic initiation mechanism is presented here with an emphasis on how recent structural and footprinting results underpin axioms of the consensus model. Along the way, we further outline some contested mechanistic issues and major open questions still to be addressed. This article is categorized under: Translation > Translation Mechanisms Translation > Translation Regulation RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications.

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Two Alternative Ways of Start Site Selection in Human Norovirus Reinitiation of Translation

Cited by 16 publications

References 54 publications

Multiple Mechanisms of Reinitiation on Bicistronic Calicivirus mRNAs

Multiple Mechanisms of Reinitiation on Bicistronic Calicivirus mRNAs

An RNA cassette from Helminthosporium victoriae virus 190S necessary and sufficient for stop/restart translation

Translation initiation by cap‐dependent ribosome recruitment: Recent insights and open questions

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