Efficient Translation of Rotavirus mRNA Requires Simultaneous Interaction of NSP3 with the Eukaryotic Translation Initiation Factor eIF4G and the mRNA 3′ End

Vende, Patrice; Piron, Maria; Castagné, Nathalie; Poncet, Didier

doi:10.1128/jvi.74.15.7064-7071.2000

Cited by 170 publications

(146 citation statements)

References 34 publications

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“…Hence, it seems probable that rotavirus mRNAs could be circularised via interactions between the RNA ends and a modified form of the eIF4F complex, of the type: capeIF4E-eIF4G-NSP3-GACC. Indeed, efficient translation of rotavirus mRNAs requires the interaction of NSP3 simultaneously with both eIF4G and the RNA 3'-end (Vende et al, 2000). Furthermore, we have found a specific10-fold stimulation of rotaviral-like mRNA translation efficiency upon the addition of NSP3 to translation reactions, reminiscent of cap-poly(A) synergy in the presence of a functional eIF4F complex (unpublished results).…”

Section: Rotavirusesmentioning

confidence: 79%

The role of mRNA 5′‐noncoding and 3′‐end sequences on 40S ribosomal subunit recruitment, and how RNA viruses successfully compete with cellular mRNAs to ensure their own protein synthesis

Kean

2003

Biology of the Cell

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This review is dedicated to Thomas Heydeman and to the memory of Leonard Zatman, the patient mentors who held my hands as I took those critical first steps into the critical world of scientific research, and who taught me so much in the process. AbstractSince the elaboration of the scanning model to explain eukaryotic translation initiation, alternative hypotheses have gained support. Cap and 5' end-independent recruitment of the 40S ribosomal subunit conferred by the presence of an internal ribosome entry segment (IRES) in the 5'UTR of the mRNA is widely accepted, and has been formally and definitively proven for a picornavirus. However, the mechanism of IRES function remains essentially a black box. Using the complex viral IRESes as model systems, approaches taken to shed light on the mystery include systematic comparisons and molecular genetic analyses. The hypothesis that actively translated mRNAs are circular, rather than linear, molecules is based on rather indirect evidence. This model has invoked a revision of the image of 40S ribosomal subunit recruitment, to include recycling from the mRNA 3'-to the 5'-end in addition to true de novo 5'-end directed entry. Biochemical and genetic studies are used to define the network of interactions necessary for efficient ribosome recruitment. This has lent weight to the concept of mRNA 5'-3' cross-talk and clarified the mechanics of how this enhances translation efficiency. These refinements and revisions to the model of translation initiation form the core of this review, with current knowledge being considered from the perspective on how host-cell translation could yield to selective viral translation via the phenomenon of translational shut-off.

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Section: Rotavirusesmentioning

confidence: 79%

The role of mRNA 5′‐noncoding and 3′‐end sequences on 40S ribosomal subunit recruitment, and how RNA viruses successfully compete with cellular mRNAs to ensure their own protein synthesis

Kean

2003

Biology of the Cell

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“…S2) shows that its activity is not strictly dependent on the initial cap-recognition event. Thus, DAZAP1 appears to function downstream from cap binding, distinguishing its activity from other characterized 39 UTR-bound activators that target this step (Vende et al 2000;Gorgoni et al 2005;Cakmakci et al 2008;Michlewski et al 2008).…”

Section: Discussionmentioning

confidence: 99%

“…1E). In conclusion, xDAZAP1 activates the translation of mRNAs only when bound, indicative of a role as an mRNAspecific activator, adding to the handful of such regulatory proteins identified (Vende et al 2000;Gorgoni et al 2005;Cakmakci et al 2008;Michlewski et al 2008). …”

Section: Laevis Dazap1 Stimulates the Translation Of Reporter Mrnasmentioning

confidence: 99%

DAZAP1, an RNA-binding protein required for development and spermatogenesis, can regulate mRNA translation

Smith¹,

Anderson²,

Smith³

et al. 2011

RNA

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DAZ-associated protein 1 (DAZAP1) is an RNA-binding protein required for normal growth, development, and fertility in mice. However, its molecular functions have not been elucidated. Here we find that Xenopus laevis and human DAZAP1, which are each expressed as short and long forms, act as mRNA-specific activators of translation in a manner that is sensitive to the number of binding sites present within the 39 UTR. Domain mapping suggests that this conserved function is mainly associated with C-terminal regions of DAZAP1. Interestingly, we find that the expression of xDAZAP1 and its polysome association are developmentally controlled, the latter suggesting that the translational activator function of DAZAP1 is regulated. However, ERK phosphorylation of DAZAP1, which can alter protein interactions with its C terminus, does not play a role in regulating its ability to participate in translational complexes. Since relatively few mRNA-specific activators have been identified, we explored the mechanism by which DAZAP1 activates translation. By utilizing reporter mRNAs with internal ribosome entry sites, we establish that DAZAP1 stimulates translation initiation. Importantly, this activity is not dependent on the recognition of the 59 cap by initiation factors, showing that it functions downstream from this frequently regulated event, but is modulated by changes in the adenylation status of mRNAs. This suggests a function in the formation of ''end-to-end'' complexes, which are important for efficient initiation, which we show to be independent of a direct interaction with the bridging protein eIF4G.

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“…SLBP and rotavirus nonstructural protein 3 (NSP3) bind unadenylated mRNAs, forming end-to-end complexes with eIF4E and eIF4G, but not with PABP (23, 33). In contrast to ICP27, SLBP fails to activate cap-independent translation (24) and NSP3-mediated activation is enhanced by the 5′ cap (33).…”

Section: Discussionmentioning

confidence: 99%

Viral and cellular mRNA-specific activators harness PABP and eIF4G to promote translation initiation downstream of cap binding

Smith

Anderson

Larralde

et al. 2017

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

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Regulation of mRNA translation is a major control point for gene expression and is critical for life. Of central importance is the complex between cap-bound eukaryotic initiation factor 4E (eIF4E), eIF4G, and poly(A) tail-binding protein (PABP) that circularizes mRNAs, promoting translation and stability. This complex is often targeted to regulate overall translation rates, and also by mRNA-specific translational repressors. However, the mechanisms of mRNA-specific translational activation by RNA-binding proteins remain poorly understood. Here, we address this deficit, focusing on a herpes simplex virus-1 protein, ICP27. We reveal a direct interaction with PABP that is sufficient to promote PABP recruitment and necessary for ICP27-mediated activation. PABP binds several translation factors but is primarily considered to activate translation initiation as part of the PABP-eIF4G-eIF4E complex that stimulates the initial cap-binding step. Importantly, we find that ICP27-PABP forms a complex with, and requires the activity of, eIF4G. Surprisingly, ICP27-PABP-eIF4G complexes act independently of the effects of PABP-eIF4G on cap binding to promote small ribosomal subunit recruitment. Moreover, we find that a cellular mRNA-specific regulator, Deleted in Azoospermia-like (Dazl), also employs the PABP-eIF4G interaction in a similar manner. We propose a mechanism whereby diverse RNA-binding proteins directly recruit PABP, in a non-poly(A) tail-dependent manner, to stimulate the small subunit recruitment step. This strategy may be particularly relevant to biological conditions associated with hypoadenylated mRNAs (e.g., germ cells/neurons) and/or limiting cytoplasmic PABP (e.g., viral infection, cell stress). This mechanism adds significant insight into our knowledge of mRNA-specific translational activation and the function of the PABP-eIF4G complex in translation initiation.D espite the importance of translational control, the mechanisms by which specific subsets of mRNAs are translationally regulated are only well defined in a handful of cases. Nevertheless, it is clear that regulation is most often mediated by factors recruited to the 3′ untranslated region (UTR) of mRNAs and frequently occurs at the level of initiation (1). Initiation is a multistep process involving several mRNA-dependent steps, each of which requires eukaryotic initiation factors (eIFs) (2). Initially, the m 7 GpppX cap is bound by eIF4F, comprising a large scaffold protein, eIF4G, bound to the cap-binding protein, eIF4E, and an RNA helicase, eIF4A. The small (40S) ribosomal subunit, initiator tRNA, and associated initiation factors are then recruited as a 43S preinitiation complex. Recruitment is facilitated by eIF4A-dependent removal of RNA secondary structure and by the interaction of 40S-associated eIF3 with eIF4G. The 43S small ribosomal subunit complex then scans the 5′ UTR to locate a start codon, recognition of which promotes release of initiation factors and joining of the large (60S) ribosomal subunit to form an 80S ribosome. Like the cap,...

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Efficient Translation of Rotavirus mRNA Requires Simultaneous Interaction of NSP3 with the Eukaryotic Translation Initiation Factor eIF4G and the mRNA 3′ End

Cited by 170 publications

References 34 publications

The role of mRNA 5′‐noncoding and 3′‐end sequences on 40S ribosomal subunit recruitment, and how RNA viruses successfully compete with cellular mRNAs to ensure their own protein synthesis

The role of mRNA 5′‐noncoding and 3′‐end sequences on 40S ribosomal subunit recruitment, and how RNA viruses successfully compete with cellular mRNAs to ensure their own protein synthesis

DAZAP1, an RNA-binding protein required for development and spermatogenesis, can regulate mRNA translation

Viral and cellular mRNA-specific activators harness PABP and eIF4G to promote translation initiation downstream of cap binding

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