Translation—A tug of war during viral infection

Rozman, Batsheva; Fisher, Tal; Stern-Ginossar, Noam

doi:10.1016/j.molcel.2022.10.012

Cited by 19 publications

(17 citation statements)

References 146 publications

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“…Many biological processes are known to cause global shutdown of translation initiation, including widespread protein misfolding in the ER, nutrient starvation and viral infection (Reid and Nicchitta, 2015; Shu et al, 2020; Walsh and Mohr, 2011). In many cases, a few mRNAs are thought to escape the global initiation shutdown, for example innate immune genes during viral infection (Rozman et al, 2023), but it has been difficult to assess translation elongation dynamics under such conditions with existing assays. We first asked whether global inhibition of translation affects elongation rates, for example by increasing the availability of charged tRNAs or elongation factors.…”

Section: Resultsmentioning

confidence: 99%

Dissecting translation elongation dynamics through ultra-long tracking of single ribosomes

Madern,

Yang,

Witteveen

et al. 2024

Preprint

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mRNA translation by ribosomes is a highly dynamic and heterogeneous process. However, current approaches cannot readily resolve individual ribosomes during translation, limiting our understanding of translation dynamics. Here, we develop an imaging approach based on Stopless-ORF circular RNAs (socRNAs) to monitor individual translating ribosomes for hours. Using the socRNA imaging technology we obtained accurate measurements of ribosome pausing on various problematic RNA sequences or induced by ribosome-targeting drugs. In addition, we identified a novel translation factor involved in translation elongation, and revealed that translocation rates of ribosomes vary, indicative of intracellular ribosomal heterogeneity. Finally, socRNAs allow very sensitive measurements of translation elongation fidelity, revealing widespread frameshifting during translation. In summary, our single-ribosome imaging approach provides a detailed view of ribosome translocation kinetics and a powerful new tool to study the translation elongation phase.

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Section: Resultsmentioning

confidence: 99%

Dissecting translation elongation dynamics through ultra-long tracking of single ribosomes

Madern,

Yang,

Witteveen

et al. 2024

Preprint

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“…Much work has been done in animal virus systems, from which two main themes have emerged: The manipulation of RNA granule numbers during infection and the re-purposing of RNA granule components for viral replication (Figure 10). In animals, viruses are challenged with a translational shutdown of the cell upon infection initiation (Rozman et al, 2022), often leading to an initial increase of SGs, before viral counter mechanisms reduce SG numbers, either through cleavage of SG components (White et al, 2007), forced translation (Montero et al, 2008) or antagonizing key signalling steps in SG formation (Khaperskyy et al, 2012). Mammarenaviruses can evade even the initial SG induction through rapid and effective suppression of SG formation (Linero et al, 2011).…”

Section: Rna Granules On a Scale From Pro-to Anti-virallearning From ...mentioning

confidence: 99%

Stress & Granules : regulation of Cauliflower mosaic virus disease in Arabidopsis thaliana

Hoffmann¹

2023

Acta Universitatis Agriculturae Sueciae

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Viruses exist in intimate relationships with the organisms they are infecting and are just as dependent on compatibility with their host’s cellular components as they are on subverting them. During any virus infection, the cells are flooded with foreign nucleic acids (DNA and/or RNA) and have learned to recognize, disarm, or eliminate them. In turn, viruses have evolved to use the cellular transcription and RNA regulatory machinery for their own benefit. Cytoplasmic RNA granules, namely Processing bodies (PBs) and Stress granules (SGs) are at the forefront of RNA regulation as they contain and store untranslated RNA and are responsive in number, size, and composition to various stresses, including virus infection. For this thesis, we have explored the role of Arabidopsis thaliana RNA granules during infection with the pararetrovirus Cauliflower mosaic virus (CaMV). We show that PB components aid virus accumulation through shielding of the viral RNA from the antiviral RNA silencing machinery (Paper I). In addition, we find that the cytoplasmic viral replication factory contains several RNA granule proteins during infection, including both, PB components and SG components. Opposite to PBs, SGs are likely antiviral and CaMV subverts their biogenesis through its multifunctional protein P6 (Paper II). In an effort to uncover novel disease determinants, we explore the variation of CaMV disease in naturally occurring populations of Arabidopsis thaliana and uncover the importance of the plant hormone abscisic acid and its homeostasis for CaMV infection, as well as a novel CaMV susceptibility factor, the ABA synthesis gene NCED9 (Paper III).

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“…Viruses lack biosynthetic capabilities and depend upon the host translation machinery for protein synthesis. To coerce the host translational machinery into synthesizing viral proteins, many positive‐sense RNA viruses have evolved various translation strategies, such as cap‐independent translation and translational recoding (Rozman et al., 2023; Stern‐Ginossar et al., 2019; Urquidi‐Camacho et al., 2020). Cap‐independent translation in plant RNA viruses lacking the 5′ cap is often mediated by internal ribosome entry sites (IRESs) and/or 3′ cap‐independent translation enhancers (CITEs).…”

Section: Introductionmentioning

confidence: 99%

Turnip mosaic virus NIb weakens the function of eukaryotic translation initiation factor 6 facilitating viral infection in Nicotiana benthamiana

Chen,

Wang,

Chen

et al. 2024

Molecular Plant Pathology

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Viruses rely completely on host translational machinery to produce the proteins encoded by their genes. Controlling translation initiation is important for gaining translational advantage in conflicts between the host and virus. The eukaryotic translation initiation factor 4E (eIF4E) has been reported to be hijacked by potyviruses for virus multiplication. The role of translation regulation in defence and anti‐defence between plants and viruses is not well understood. We report that the transcript level of eIF6 was markedly increased in turnip mosaic virus (TuMV)‐infected Nicotiana benthamiana. TuMV infection was impaired by overexpression of N. benthamiana eIF6 (NbeIF6) either transiently expressed in leaves or stably expressed in transgenic plants. Polysome profile assays showed that overexpression of NbeIF6 caused the accumulation of 40S and 60S ribosomal subunits, the reduction of polysomes, and also compromised TuMV UTR‐mediated translation, indicating a defence role for upregulated NbeIF6 during TuMV infection. However, the polysome profile in TuMV‐infected leaves was not identical to that in leaves overexpressing NbeIF6. Further analysis showed that TuMV NIb protein, the RNA‐dependent RNA polymerase, interacted with NbeIF6 and interfered with its effect on the ribosomal subunits, suggesting that NIb might have a counterdefence role. The results propose a possible regulatory mechanism at the translation level during plant–virus interaction.

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Translation—A tug of war during viral infection

Cited by 19 publications

References 146 publications

Dissecting translation elongation dynamics through ultra-long tracking of single ribosomes

Dissecting translation elongation dynamics through ultra-long tracking of single ribosomes

Stress & Granules : regulation of Cauliflower mosaic virus disease in Arabidopsis thaliana

Turnip mosaic virus NIb weakens the function of eukaryotic translation initiation factor 6 facilitating viral infection in Nicotiana benthamiana

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