Ribosomal protein RACK1 enhances translation of poliovirus and other viral IRESs

LaFontaine, Ethan; Miller, Clare M.; Permaul, Natasha; Martin, Elliot T.; Fuchs, Gabriele

doi:10.1016/j.virol.2020.03.004

Cited by 22 publications

(25 citation statements)

References 69 publications

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“…Our approach therefore required a cell line that would provide sufficient material but which retained this homeostatic balance. HAP1 cells are a fibroblast-like nearhaploid cell line that we previously used to generate a RACK1 knockout line (Jha et al, 2017), and which do not contain appreciable amounts of extra-ribosomal RACK1 or other RPs (LaFontaine et al, 2020). Studies of these cells by other groups have shown that exogenous re-expression of RACK1 rescues phenotypes studied and, importantly, RACK1 is tightly bound to the ribosome in these cells (Johnson et al, 2019;LaFontaine et al, 2020).…”

Section: Resultsmentioning

confidence: 99%

“…HAP1 cells are a fibroblast-like nearhaploid cell line that we previously used to generate a RACK1 knockout line (Jha et al, 2017), and which do not contain appreciable amounts of extra-ribosomal RACK1 or other RPs (LaFontaine et al, 2020). Studies of these cells by other groups have shown that exogenous re-expression of RACK1 rescues phenotypes studied and, importantly, RACK1 is tightly bound to the ribosome in these cells (Johnson et al, 2019;LaFontaine et al, 2020). In line with this, we found that when RACK1-eGFP was transduced into parental HAP1 cells only low levels of expression could be achieved relative to the endogenous form, and only equivalently small reductions in endogenous RACK1 were observed in RACK1-eGFP-expressing lines (Fig.…”

Section: Resultsmentioning

confidence: 99%

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Proteomic and mechanistic dissection of the poxvirus-customized ribosome

DiGiuseppe

Rollins

Astar

et al. 2020

Journal of Cell Science

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Ribosomes are often viewed as protein synthesis machines that lack intrinsic regulatory capacity. However, studies have established that ribosomes can functionally diversify through changes in the composition of, or post-translational modifications to ribosomal subunit proteins (RPs). We recently found that poxviruses phosphorylate unique sites in the RP, Receptor for Activated C Kinase 1 (RACK1) to enhance viral protein synthesis. Here, we developed approaches for large-scale proteomic analysis of ribosomes isolated from cells infected with different viruses. Beyond RACK1, we identified additional phosphorylation events within RPS2 and RPS28 that arise during poxvirus infection, but not other viruses tested. The modified sites lie within unstructured loop domains that position around the mRNA entry and exit channel, respectively, and site-substitution mutants revealed that each modified residue contributed differently to poxvirus replication. Our findings reveal the broader extent to which poxviruses customize host ribosomes and provide new insights into how ribosomes can functionally diversify.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Proteomic and mechanistic dissection of the poxvirus-customized ribosome

DiGiuseppe

Rollins

Astar

et al. 2020

Journal of Cell Science

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“…While depletion is often efficient, residual protein levels make it difficult to distinguish preferential from specialized translation. Studies using complete knockout cell lines provide evidence supporting the preferential translation model, as loss of eS25 or RACK1 decreased DV, WNV, ZIKV, and PV genome translation respectively (LaFontaine et al, 2020; Marceau et al, 2016). Based on the current evidence, the preferential translation model appears to be supported, however, coexisting mechanisms cannot yet be ruled out.…”

Section: Viruses Exploit the Function Of Specific Ribosomal Proteinsmentioning

confidence: 94%

Fatal attraction: The roles of ribosomal proteins in the viral life cycle

2020

Self Cite

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Upon viral infection of a host cell, each virus starts a program to generate many progeny viruses. Although viruses interact with the host cell in numerous ways, one critical step in the virus life cycle is the expression of viral proteins, which are synthesized by the host ribosomes in conjunction with host translation factors. Here we review different mechanisms viruses have evolved to effectively seize host cell ribosomes, the roles of specific ribosomal proteins and their posttranslational modifications on viral RNA translation, or the cellular response to infection. We further highlight ribosomal proteins with extra‐ribosomal function during viral infection and put the knowledge of ribosomal proteins during viral infection into the larger context of ribosome‐related diseases, known as ribosomopathies. This article is categorized under: Translation > Translation Mechanisms Translation > Translation Regulation

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“…3 ). Also, some IRES functions, like those found in polio, HCV or dicistroviridae , have been shown to be regulated by small ribosomal proteins such as RACK1 and RPS25 [ [169] , [170] , [171] , [172] , [173] ] ( Fig. 3 ).…”

Section: The Translation Battlefieldmentioning

confidence: 99%

Roadblocks and fast tracks: How RNA binding proteins affect the viral RNA journey in the cell

Girardi¹,

Pfeffer²,

Baumert³

et al. 2021

Seminars in Cell & Developmental Biology

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As obligate intracellular parasites with limited coding capacity, RNA viruses rely on host cells to complete their multiplication cycle. Viral RNAs (vRNAs) are central to infection. They carry all the necessary information for a virus to synthesize its proteins, replicate and spread and could also play essential non-coding roles. Regardless of its origin or tropism, vRNA has by definition evolved in the presence of host RNA Binding Proteins (RBPs), which resulted in intricate and complicated interactions with these factors. While on one hand some host RBPs recognize vRNA as non-self and mobilize host antiviral defenses, vRNA must also co-opt other host RBPs to promote viral infection. Focusing on pathogenic RNA viruses, we will review important scenarios of RBP-vRNA interactions during which host RBPs recognize, modify or degrade vRNAs. We will then focus on how vRNA hijacks the largest ribonucleoprotein complex (RNP) in the cell, the ribosome, to selectively promote the synthesis of its proteins. We will finally reflect on how novel technologies are helping in deepening our understanding of vRNA-host RBPs interactions, which can be ultimately leveraged to combat everlasting viral threats.

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Ribosomal protein RACK1 enhances translation of poliovirus and other viral IRESs

Cited by 22 publications

References 69 publications

Proteomic and mechanistic dissection of the poxvirus-customized ribosome

Proteomic and mechanistic dissection of the poxvirus-customized ribosome

Fatal attraction: The roles of ribosomal proteins in the viral life cycle

Roadblocks and fast tracks: How RNA binding proteins affect the viral RNA journey in the cell

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