Poly(A)-binding protein (PABP): a common viral target

Smith, Richard; Gray, Nicola K.

doi:10.1042/bj20091571

Cited by 78 publications

(103 citation statements)

References 111 publications

(163 reference statements)

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“…Thus, although our analysis has allowed the effects of the PABP-eIF4G complex on downstream events to be recognized, informing on both mRNA-specific activation and the role of the PABP-eIF4G complex during initiation, it does not exclude that ICP27/Dazl-PABP-eIF4G complexes can also enhance cap binding. Our work highlights a way in which viruses target PABP function to hijack the host translational machinery (20). However, because HSV-1 mRNAs are capped and polyadenylated (9), the question is raised of why their translation should require an additional means of PABP recruitment.…”

Section: Discussionmentioning

confidence: 99%

“…2A). Dual binding sites have been described for several other PABP partner proteins (20). Because both ICP27 and PABP are RNA-binding proteins, RRM1-2Rd (Y56V, F142V) (16), an RNA-bindingdeficient mutant of RRM1-2, was used to confirm further that their interaction is not RNA-mediated ( Fig.…”

Section: Significancementioning

confidence: 99%

“…Thus, to ascertain whether it is functionally targeted in ICP27-mediated translational activation, modified tether-function assays were undertaken in which mRNAs encoding picornavirus 2A protease (2Apro) or U1A (negative control) were coinjected with reporter mRNAs. Cleavage by 2Apro separates an N-terminal part of eIF4G that binds eIF4E and PABP from the C-terminal part that binds RNA, eIF4A, and 40S subunit-associated eIF3 (20). A lacZ mRNA containing the eIF4G-independent, 2Apro-insensitive CSFV IRES served as a critical internal control (Figs.…”

Section: Icp27 Stimulates Initiation Of Translation Independently Of Thementioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Significancementioning

confidence: 99%

Section: Icp27 Stimulates Initiation Of Translation Independently Of Thementioning

confidence: 99%

See 1 more Smart Citation

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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“…Clade 5 proteins showed high homologies to several poly-A binding proteins (PABPs) that are important for RNA stability and translation. As central regulators of gene expression, PABPs are targeted by a variety of DNA and RNA viruses, which leads to changes in complex formation, RNA stability, and localization (Smith and Gray, 2010). RBPs belonging to clades 6 and 9 showed motif organization similar to the hnRNP Q-like proteins that are important for mRNA splicing (Singh, 2007).…”

Section: Discussionmentioning

confidence: 99%

Phylogenetic and Expression Analysis of RNA-binding Proteins with Triple RNA Recognition Motifs in Plants

Peal¹,

Jambunathan²,

Mahalingam³

2011

Molecules and Cells

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The superfamily of RNA binding proteins (RBPs) is vastly expanded in plants compared to other eukaryotes. A subfamily of RBPs that contain three RNA recognition motifs (RRMs) from the Arabidopsis (24), rice (19) and poplar (37) genomes was analyzed in this study. Phylogenetic analysis with full-length protein sequences of 80 RBPs identified nine clades. The largest clade, comprising 23 members, showed high homology to human RBPs involved in oxidative signaling. Digital northern analysis revealed that Arabidopsis RBPs are transcriptionally responsive to biotic, abiotic and hormonal treatments. Northern blot analysis of eight Arabidopsis RBPs belonging to the tobacco RBP45/47 family showed that these genes respond to ozone stress. AtRBP45b, which shows closest homology to the yeast oxidative stress regulatory protein, CSX1, was expressed in multiple tissues. Two novel splice variant forms of AtRBP45b were identified by 3'RACE analysis. Based on RT-PCR, splice variant AtRBP45b-SV1 was observed only in response to mechanical wounding caused by pathogen or chemical infiltrations and was not detectable in response to salt or temperature stress. Electrophoretic mobility shift assay demonstrated that recombinant full-length and splice variant forms of AtRBP45b bound synthetic RNA. Identifying in vivo RNA targets of AtRBP45b will aid in determining the precise functional role of these proteins during oxidative signaling.

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“…This second domain is absent in mammals and yeast PABP. PABP is also implicated in viral replication (Smith and Gray, 2010) and plant PABP was shown to interact with the reverse transcriptase of turnip mosaic virus (TuMV) (Dufresne et al, 2008) and with the 3'UTR of tobacco etch virus (TEV) to promote internal initiation (Khan et al, 2008;Khan et al, 2009;Yumak et al, 2010;Iwakawa et al, 2012).…”

Section: Poly(a) Binding Proteinmentioning

confidence: 99%

Mechanism of Cytoplasmic mRNA Translation

Browning

Bailey‐Serres

2015

The Arabidopsis Book

190

220

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Protein synthesis is a fundamental process in gene expression that depends upon the abundance and accessibility of the mRNA transcript as well as the activity of many protein and RNA-protein complexes. Here we focus on the intricate mechanics of mRNA translation in the cytoplasm of higher plants. This chapter includes an inventory of the plant translational apparatus and a detailed review of the translational processes of initiation, elongation, and termination. The majority of mechanistic studies of cytoplasmic translation have been carried out in yeast and mammalian systems. The factors and mechanisms of translation are for the most part conserved across eukaryotes; however, some distinctions are known to exist in plants. A comprehensive understanding of the complex translational apparatus and its regulation in plants is warranted, as the modulation of protein production is critical to development, environmental plasticity and biomass yield in diverse ecosystems and agricultural settings.

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Poly(A)-binding protein (PABP): a common viral target

Cited by 78 publications

References 111 publications

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

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

Phylogenetic and Expression Analysis of RNA-binding Proteins with Triple RNA Recognition Motifs in Plants

Mechanism of Cytoplasmic mRNA Translation

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