Functional Interaction between JC Virus Late Regulatory Agnoprotein and Cellular Y-Box Binding Transcription Factor, YB-1

Safak, Mahmut; Sadowska, Beata; Barrucco, Robert; Khalili, Kamel

doi:10.1128/jvi.76.8.3828-3838.2002

Cited by 58 publications

(80 citation statements)

References 49 publications

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“…Agnoprotein is a 71 aa multi-functional protein with numerous reported protein-protein interactions (Darbinyan et al, 2004;Endo et al, 2003;Johannessen et al, 2008;Safak et al, 2002;Suzuki et al, 2005). It also retains a central hydrophobic TMD which, along with an N-terminal region, is required for ER/plasma membrane localization and membrane integration (Suzuki et al, 2010), and forms stable oligomers within infected cells (Coric et al, 2014;Saribas et al, 2011Saribas et al, , 2013Suzuki et al, 2010).…”

Section: Dna Virus Viroporinsmentioning

confidence: 99%

Viroporins: structure, function and potential as antiviral targets

Scott

Griffin

2015

Journal of General Virology

120

146

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The channel-forming activity of a family of small, hydrophobic integral membrane proteins termed 'viroporins' is essential to the life cycles of an increasingly diverse range of RNA and DNA viruses, generating significant interest in targeting these proteins for antiviral development. Viroporins vary greatly in terms of their atomic structure and can perform multiple functions during the virus life cycle, including those distinct from their role as oligomeric membrane channels. Recent progress has seen an explosion in both the identification and understanding of many such proteins encoded by highly significant pathogens, yet the prototypic M2 proton channel of influenza A virus remains the only example of a viroporin with provenance as an antiviral drug target. This review attempts to summarize our current understanding of the channel-forming functions for key members of this growing family, including recent progress in structural studies and drug discovery research, as well as novel insights into the life cycles of many viruses revealed by a requirement for viroporin activity. Ultimately, given the successes of drugs targeting ion channels in other areas of medicine, unlocking the therapeutic potential of viroporins represents a valuable goal for many of the most significant viral challenges to human and animal health.

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Section: Dna Virus Viroporinsmentioning

confidence: 99%

Viroporins: structure, function and potential as antiviral targets

Scott

Griffin

2015

Journal of General Virology

120

146

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“…Interestingly, a single member of the Y-box family can regulate multiple processes. For example, the best-studied Y-box protein, YB-1 (p50), modulates transcription (Mertens et al 1997;Norman et al 2001;Safak et al 2002), pre-mRNA splicing (Stickeler et al 2001), mRNA stability Evdokimova et al 2001), and translation (Sommerville andLadomery 1996, Evdokimova et al 1998;Pisarev et al 2002). Furthermore, YB-1 acts as a gene-specific transcriptional transactivator or repressor (Matsumoto and Wollfe 1998), and can even have opposite effects on the same promoter depending on cell type (Mertens et al 1997).…”

Section: Introductionmentioning

confidence: 99%

“…Y-box proteins comprise a family of DNA-and RNA-binding proteins that are involved in numerous and diverse biological processes (for review, see Graumann and Marahiel 1998). Members of this family have been shown to regulate gene expression at transcriptional (Mertens et al 1997;Norman et al 2001;Safak et al 2002), posttranscriptional (Grosset et al 2000;Evdokimova et al 2001;Stickeler et al 2001), and translational levels (Sommerville and Ladomery 1996;Evdokimova et al 1998;Pisarev et al 2002). In some cases, Y-box proteins have been reported to act through the promotion of DNA and RNA annealing (Skabkin et al 2001) or by acting as RNA chaperones to destabilize secondary structures (Jiang et al 1997;Bae et al 2000).…”

Section: Introductionmentioning

confidence: 99%

RBP16 is a multifunctional gene regulatory protein involved in editing and stabilization of specific mitochondrial mRNAs in Trypanosoma brucei

Pelletier¹,

Read²

2003

RNA

132

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RBP16 is a Trypanosoma brucei mitochondrial RNA-binding protein that associates with guide RNAs (gRNAs), mRNAs, and ribosomal RNAs. Based on its inclusion in the multifunctional Y-box protein family and its ability to bind multiple RNA classes, we hypothesized that RBP16 plays a role in diverse aspects of mitochondrial gene regulation. To gain insight into RBP16 function, we generated cells expressing less than 10% of wild-type RBP16 levels by tetracycline-regulated RNA interference (RNAi). Poisoned primer extension analyses revealed that edited, but not unedited, CYb mRNA is reduced by ∼98% in tetracycline-induced RBP16 RNAi cells, suggesting that RBP16 is critical for CYb RNA editing. The down-regulation of CYb editing in RBP16 RNAi transfectants apparently entails a defect in gRNA utilization, as gCYb[560] abundance is similar in uninduced and induced cells. We observed a surprising degree of specificity regarding the ability of RBP16 to modulate editing, as editing of mRNAs other than CYb is not significantly affected upon RBP16 disruption. However, the abundance of the never edited mitochondrial RNAs COI and ND4 is reduced by 70%-80% in RBP16 RNAi transfectants, indicating an additional role for RBP16 in the stabilization of these mRNAs. Analysis of RNAs bound to RBP16 immunoprecipitated from wild-type cells reveals that RBP16 is associated with multiple gRNA sequence classes in vivo, including those whose abundance and usage appear unaffected by RBP16 disruption. Overall, our results indicate that RBP16 is an accessory factor that regulates the editing and stability of specific populations of mitochondrial mRNAs.

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“…The RBP16 protein contains a conserved nucleic acid binding domain known as the cold shock domain (CSD) at its N terminus, placing RBP16 as a member of the eukaryotic Y-box protein family (Graumann and Marahiel 1996;Hayman and Read 1999). Y-box proteins comprise a family of DNA and RNA binding proteins involved in pleiotropic biological functions, including regulation of gene expression at the transcriptional (Mertens et al 1997;Norman et al 2001;Safak et al 2002), post-transcriptional (Grosset et al 2000;Evdokimova et al 2001;Stickeler et al 2001), and translational levels (Sommerville and Ladomery 1996;Evdokimova et al 1998;Pisarev et al 2002). In addition, some CSD-containing proteins have been reported to facilitate nucleic acid annealing (Skabkin et al 2001) or to destabilize RNA secondary structure by acting as RNA chaperones (Jiang et al 1999;Bae et al 2000).…”

Section: Introductionmentioning

confidence: 99%

RBP16 stimulates trypanosome RNA editing in vitro at an early step in the editing reaction

Miller¹,

Halbig²,

Cruz‐Reyes³

et al. 2006

RNA

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RBP16 is an abundant RNA binding protein from Trypanosoma brucei mitochondria that affects both RNA editing and stability. We report here experiments aimed at elucidating the mechanism of RBP16 function in RNA editing. In in vitro RNA editing assays, recombinant RBP16 is able to significantly stimulate insertion editing of both CYb and A6 pre-mRNAs. Enhancement of in vitro editing activity occurs at, or prior to, the step of pre-mRNA cleavage, as evidenced by increased accumulation of premRNA 39 cleavage products in the presence of RBP16. Mutated RBP16 that is severely compromised in cold shock domain (CSD)-mediated RNA binding was able to enhance editing to levels comparable to the wild-type protein in some assays at the highest RBP16 levels tested. However, at low RBP16 concentrations or in assays with native, oligo(U)-tail-bearing gRNAs, editing stimulation by mutant RBP16 was somewhat compromised. Together, these results indicate that both the N-terminal CSD and C-terminal RGG RNA binding domains of RBP16 are required for maximal editing stimulation. Finally, the relaxed specificity of RBP16 for stimulation of both CYb and A6 editing in vitro implicates additional specificity factors that account for the strict CYb specificity of RBP16 action in editing in vivo. Our results constitute the first report of any putative RNA editing accessory factor eliciting an effect on editing in vitro. Overall, these results support a novel accessory role for RBP16 in U insertion editing.

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Functional Interaction between JC Virus Late Regulatory Agnoprotein and Cellular Y-Box Binding Transcription Factor, YB-1

Cited by 58 publications

References 49 publications

Viroporins: structure, function and potential as antiviral targets

Viroporins: structure, function and potential as antiviral targets

RBP16 is a multifunctional gene regulatory protein involved in editing and stabilization of specific mitochondrial mRNAs in Trypanosoma brucei

RBP16 stimulates trypanosome RNA editing in vitro at an early step in the editing reaction

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