RACK1 Controls IRES-Mediated Translation of Viruses

Majzoub, Karim; Hafirassou, Mohamed Lamine; Meignin, Carine; Goto, Ayumu; Marzi, Stefano; Fedorova, Antonina A.; Verdier, Yann; Vinh, Joëlle; Hoffmann, Jules A.; Martin, Franck; Baumert, Thomas F.; Schuster, Catherine; Imler, Jean‐Luc

doi:10.1016/j.cell.2014.10.041

Cited by 163 publications

(202 citation statements)

References 83 publications

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“…For instance, the loosely bound eIF3j subunit must be removed from its entry channel location prior to stable accommodation of the HCV IRES mRNA start codon within the P site, possibly promoted by recruitment of the eIF2-TC [123]. Additionally, the eIF3d subunit resides on the rear side of the 40S subunit head (in canonical 43S complexes) near ribosomal protein RACK1, which is intriguingly required for IRES-mediated, but not canonical, translation [124]. Rather than a direct physical interaction between the HCV IRES and RACK1, one possibility is that RACK1 makes remote interactions to the IRES mediated by eIF3.…”

Section: (D) the Structural And Functional Basis Of Hcv Ires : Eif3 Imentioning

confidence: 99%

Dynamics of IRES-mediated translation

Johnson

Grosely

Petrov

et al. 2017

Phil. Trans. R. Soc. B

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One contribution of 12 to a theme issue 'Perspectives on the ribosome'. Viral internal ribosome entry sites (IRESs) are unique RNA elements, which use stable and dynamic RNA structures to recruit ribosomes and drive protein synthesis. IRESs overcome the high complexity of the canonical eukaryotic translation initiation pathway, often functioning with a limited set of eukaryotic initiation factors. The simplest types of IRESs are typified by the cricket paralysis virus intergenic region (CrPV IGR) and hepatitis C virus (HCV) IRESs, both of which independently form high-affinity complexes with the small (40S) ribosomal subunit and bypass the molecular processes of cap-binding and scanning. Owing to their simplicity and ribosomal affinity, the CrPV and HCV IRES have been important models for structural and functional studies of the eukaryotic ribosome during initiation, serving as excellent targets for recent technological breakthroughs in cryogenic electron microscopy (cryo-EM) and single-molecule analysis. High-resolution structural models of ribosome : IRES complexes, coupled with dynamics studies, have clarified decades of biochemical research and provided an outline of the conformational and compositional trajectory of the ribosome during initiation. Here we review recent progress in the study of HCV-and CrPV-type IRESs, highlighting important structural and dynamics insights and the synergy between cryo-EM and single-molecule studies.This article is part of the themed issue 'Perspectives on the ribosome'.

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Section: (D) the Structural And Functional Basis Of Hcv Ires : Eif3 Imentioning

confidence: 99%

Dynamics of IRES-mediated translation

Johnson

Grosely

Petrov

et al. 2017

Phil. Trans. R. Soc. B

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“…Previous studies have revealed that insect susceptibility to viral infection is determined by host factors, which either facilitate (6,7) or restrict viral replication (8)(9)(10). In addition, the bacterial flora, particularly endosymbiotic Wolbachia strains, modifies susceptibility to viral infections (11,12).…”

mentioning

confidence: 99%

Cytokine Diedel and a viral homologue suppress the IMD pathway in Drosophila

Lamiable

Kellenberger

Kemp

et al. 2016

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

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111

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Viruses are obligatory intracellular parasites that suffer strong evolutionary pressure from the host immune system. Rapidly evolving viral genomes can adapt to this pressure by acquiring genes that counteract host defense mechanisms. For example, many vertebrate DNA viruses have hijacked cellular genes encoding cytokines or cytokine receptors to disrupt host cell communication. Insect viruses express suppressors of RNA interference or apoptosis, highlighting the importance of these cell intrinsic antiviral mechanisms in invertebrates. Here, we report the identification and characterization of a family of proteins encoded by insect DNA viruses that are homologous to a 12-kDa circulating protein encoded by the virus-induced Drosophila gene diedel (die). We show that die mutant flies have shortened lifespan and succumb more rapidly than controls when infected with Sindbis virus. This reduced viability is associated with deregulated activation of the immune deficiency (IMD) pathway of host defense and can be rescued by mutations in the genes encoding the homolog of IKKγ or IMD itself. Our results reveal an endogenous pathway that is exploited by insect viruses to modulate NF-κB signaling and promote fly survival during the antiviral response.

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“…CD81 29 , RACK1 30 , PI4KIIIα [31][32][33] , and ApoE 8,12,17,34 are important cellular factors in HCV entry, IRES-mediated translation, RNA replication, and assembly, respectively. To determine the specific stage of the HCV life cycle that requires CIDEB, a panel of siRNAs targeting these genes was used.…”

Section: Resultsmentioning

confidence: 99%