Novel viral translation strategies

Au, Hilda H. T.; Jan, Eric

doi:10.1002/wrna.1246

Cited by 33 publications

(32 citation statements)

References 178 publications

(253 reference statements)

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“…In contrast to this mechanism used by the vast majority of cellular mRNAs, various viral RNAs have evolved alternative mechanisms to initiate translation [2,3,4]. A paradigmatic example is provided by picornaviruses, which subvert the host translational machinery to promote translation of the viral genome using a cap-independent mechanism.…”

Section: Introductionmentioning

confidence: 98%

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Structural insights into viral IRES-dependent translation mechanisms

Lozano

Martínez‐Salas

2015

Current Opinion in Virology

140

153

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A diverse group of viruses subvert the host translational machinery to promote viral genome translation. This process often involves altering canonical translation initiation factors to repress cellular protein synthesis while viral proteins are efficiently synthesized. The discovery of this strategy in picornaviruses, which is based on the use of internal ribosome entry site (IRES) elements, opened new avenues to study alternative translational control mechanisms evolved in different groups of RNA viruses. IRESs are cis-acting RNA sequences that adopt three-dimensional structures and recruit the translation machinery assisted by a subset of translation initiation factors and various RNA binding proteins. However, IRESs present in the genome of different RNA viruses perform the same function despite lacking conservation of primary sequence and secondary RNA structure, and differing in host factor requirement to recruit the translation machinery. Evolutionary conserved motifs tend to preserve sequences impacting on RNA structure and RNA-protein interactions important for IRES function. While some motifs are found in various picornavirus IRESs, others occur only in one type reflecting specialized factor requirements. This review is focused to describe recent advances on the principles and RNA structure features of picornavirus IRESs.

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Section: Introductionmentioning

confidence: 98%

“…Initiation of translation in a diverse group of RNA viruses differs from the bulk of cellular mRNAs in many ways [1,2]. Most cellular mRNAs initiate translation by a mechanism that depends on the recognition of the m 7 G(5 0 )ppp(5 0 )N structure (termed cap) located at the 5 0 end of mRNAs.…”

Section: Introductionmentioning

confidence: 99%

Structural insights into viral IRES-dependent translation mechanisms

Lozano

Martínez‐Salas

2015

Current Opinion in Virology

140

153

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“…Particularly, host eIF4E is expressed at low levels in most cell types (29), and several viruses have evolved mechanisms to control eIF4E availability or assembly of the eIF4F complex (18,30). Previous studies on JUNV and TCRV have reported that while the functional activity of eIF4GI and eIF4A is required, eIF4E is unessential for virus multiplication (23).…”

Section: Discussionmentioning

confidence: 99%

“…Picornaviruses, retroviruses, and caliciviruses, for example, code for proteases that cleave host translation factors, including eIF4G, thus preventing host cap-dependent translation. Viral mRNAs translation remains unaffected because of the usage of internal ribosome entry sites (IRES) to initiate the process via a cap-independent mechanism (18)(19)(20). Differently, rotavirus nonstructural protein NSP3 binds to a consensus sequence at the 3= UTR of the capped and nonpolyadenylated viral mRNAs and interacts with eIF4G at the PABP-binding site, impairing the translation of cellular mRNAs (21).…”

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confidence: 99%

Regulation of Tacaribe Mammarenavirus Translation: Positive 5′ and Negative 3′ Elements and Role of Key Cellular Factors

Foscaldi

D'antuono

Noval

et al. 2017

J Virol

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Mammarenaviruses are enveloped viruses with a bisegmented negativestranded RNA genome that encodes the nucleocapsid protein (NP), the envelope glycoprotein precursor (GPC), the RNA polymerase (L), and a RING matrix protein (Z). Viral proteins are synthesized from subgenomic mRNAs bearing a capped 5= untranslated region (UTR) and lacking 3= poly(A) tail. We analyzed the translation strategy of Tacaribe virus (TCRV), a prototype of the New World mammarenaviruses. A virus-like transcript that carries a reporter gene in place of the NP open reading frame and transcripts bearing modified 5= and/or 3= UTR were evaluated in a cellbased translation assay. We found that the presence of the cap structure at the 5= end dramatically increases translation efficiency and that the viral 5= UTR comprises stimulatory signals while the 3= UTR,specifically the presence of a terminal CϩG-rich sequence and/or a stem-loop structure, down-modulates translation. Additionally, translation was profoundly reduced in eukaryotic initiation factor (eIF) 4G-inactivated cells, whereas depletion of intracellular levels of eIF4E had less impact on virus-like mRNA translation than on a cell-like transcript. Translation efficiency was independent of NP expression or TCRV infection. Our results indicate that TCRV mRNAs are translated using a cap-dependent mechanism, whose efficiency relies on the interplay between stimulatory signals in the 5= UTR and a negative modulatory element in the 3= UTR. The low dependence on eIF4E suggests that viral mRNAs may engage yet-unknown noncanonical host factors for a cap-dependent initiation mechanism.IMPORTANCE Several members of the Arenaviridae family cause serious hemorrhagic fevers in humans. In the present report, we describe the mechanism by which Tacaribe virus, a prototypic nonpathogenic New World mammarenavirus, regulates viral mRNA translation. Our results highlight the impact of untranslated sequences and key host translation factors on this process. We propose a model that explains how viral mRNAs outcompete cellular mRNAs for the translation machinery. A better understanding of the mechanism of translation regulation of this virus can provide the bases for the rational design of new antiviral tools directed to pathogenic arenaviruses.KEYWORDS arenavirus, mRNA, translation T he Arenaviridae family comprises the genera Reptarenavirus and Mammarenavirus; the latter, which includes important human pathogens, is further subdivided based on phylogeny, serological properties, and geographical distribution into two main groups: the Old World (OW) and New World (NW) viruses (1). Tacaribe mammarenavirus

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“…In contrast, the picornavirus genomic RNA initiate translation internally through a cis-acting region designated internal ribosome entry site (IRES) element, using a cap-independent mechanism [2,3]. Moreover, IRESs also drive translation initiation in hepatitis C virus (HCV), pestiviruses, dicistroviruses, retroviruses, and some plant RNA viruses [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

RNA–protein interaction methods to study viral IRES elements

Francisco‐Velilla

Fernandez-Chamorro

Lozano

et al. 2015

Methods

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a b s t r a c tTranslation control often takes place through the mRNA untranslated regions, involving direct interactions with RNA-binding proteins (RBPs). Internal ribosome entry site elements (IRESs) are cis-acting RNA regions that promote translation initiation using a cap-independent mechanism. A subset of positive-strand RNA viruses harbor IRESs as a strategy to ensure efficient viral protein synthesis. IRESs are organized in modular structural domains with a division of functions. However, viral IRESs vary in nucleotide sequence, secondary RNA structure, and transacting factor requirements. Therefore, in-depth studies are needed to understand how distinct types of viral IRESs perform their function. In this review we describe methods to isolate and identify RNA-binding proteins important for IRES activity, and to study the impact of RNA structure and RNA-protein interactions on IRES activity.

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Novel viral translation strategies

Cited by 33 publications

References 178 publications

Structural insights into viral IRES-dependent translation mechanisms

Structural insights into viral IRES-dependent translation mechanisms

Regulation of Tacaribe Mammarenavirus Translation: Positive 5′ and Negative 3′ Elements and Role of Key Cellular Factors

RNA–protein interaction methods to study viral IRES elements

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