Kaposi’s Sarcoma-Associated Herpesvirus ORF57 Protein: Exploiting All Stages of Viral mRNA Processing

Schumann, Sophie; Jackson, Brian R.; Baquero-Pérez, Belinda; Whitehouse, Adrian

doi:10.3390/v5081901

Cited by 22 publications

(26 citation statements)

References 132 publications

(187 reference statements)

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“…Recently, the HPV-16 E2 protein was reported to regulate the usage of the proximal polyadenylation cisacting elements in the middle of its genome by modulating the recruitment of the polyadenylation machinery to this site (44,45). In addition, viral proteins such as herpes simplex virus 1 (HSV-1) ICP27 (46,47), the Kaposi sarcoma-associated herpesvirus (KSHV) ORF57 protein (48)(49)(50), and the human cytomegalovirus protein UL69 (51,52) have been shown to modulate the processing of HSV, KSHV, and HCMV transcripts, respectively. Because of its specificity, NP1's function and how it regulates RNA processing may be different from these examples.…”

Section: Discussionmentioning

confidence: 99%

NP1 Protein of the Bocaparvovirus Minute Virus of Canines Controls Access to the Viral Capsid Genes via Its Role in RNA Processing

Fasina

Dong

Pintel

2016

J Virol

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Minute virus of canines (MVC) is an autonomous parvovirus in the genusBocaparvovirus. It has a single promoter that generates a single pre-mRNA processed via alternative splicing and alternative polyadenylation to produce at least 8 mRNA transcripts. MVC contains two polyadenylation sites, one at the right-hand end of the genome, (pA)d, and another complex site, (pA)p, within the capsid-coding region. During viral infection, the mRNAs must extend through (pA)p and undergo additional splicing of the immediately upstream 3D⁄3A intron to access the capsid gene. MVC NP1 is a 22-kDa nuclear phosphoprotein unique to the genus Bocaparvovirus of the Parvovirinae which we have shown governs suppression of (pA)p independently of viral genome replication. We show here that in addition to suppression of (pA)p, NP1 is also required for the excision of the MVC 3D⁄3A intron, independently of its effect on alternative polyadenylation. Mutations of the arginine⁄serine (SR) di-repeats within the intrinsically disordered amino terminus of NP1 are required for splicing of the capsid transcript but not suppression of polyadenylation at (pA)p. 3=-end processing of MVC mRNAs at (pA)p is critical for viral genome replication and the optimal expression of NP1 and NS1. Thus, a finely tuned balance between (pA)p suppression and usage is necessary for efficient virus replication. NP1 is the first parvovirus protein implicated in RNA processing. Its characterization reveals another way that parvoviruses govern access to their capsid protein genes, namely, at the RNA level, by regulating the essential splicing of an intron and the suppression of an internal polyadenylation site. IMPORTANCEThe Parvovirinae are small nonenveloped icosahedral viruses that are important pathogens in many animal species, including humans. Although parvoviruses have only subtle early-to-late expression shifts, they all regulate access to their capsid genes. Minute virus of canines (MVC) is an autonomous parvovirus in the genusBocaparvovirus. It has a single promoter generating a single pre-mRNA which is processed via alternative splicing and alternative polyadenylation to generate at least 8 mRNA transcripts. MVC contains two polyadenylation sites, one at the right-hand end of the genome, (pA)d, and another, (pA)p, within the capsid-coding region. It had not been clear how the potent internal polyadenylation motif is suppressed to allow processing, export, and accumulation of the spliced capsid protein-encoding mRNAs. We show here that MVC NP1, the first parvovirus protein to be implicated in RNA processing, governs access to the MVC capsid gene by facilitating splicing and suppressing internal polyadenylation of MVC pre-mRNAs. M inute virus of canines (MVC) is an autonomous parvovirus in the genusBocaparvovirus. Infection in young dogs can result in neonatal mortality (1) and respiratory and gastrointestinal distress (2) and can cause infertility and stillbirths in adult pregnant female dogs (3). The parvovirus genus Bocaparvovirus has 12 currently known...

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Section: Discussionmentioning

confidence: 99%

NP1 Protein of the Bocaparvovirus Minute Virus of Canines Controls Access to the Viral Capsid Genes via Its Role in RNA Processing

Fasina

Dong

Pintel

2016

J Virol

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“…ORF57 is a multifunctional protein which ensures efficient late viral gene expression on many levels (Table ). However, to date it remains largely elusive how ORF57 recognizes and selects the majority of viral RNAs.…”

Section: Introductionmentioning

confidence: 99%

The KSHV RNA regulator ORF57: target specificity and its role in the viral life cycle

Vogt

Bohne

2016

WIREs RNA

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Kaposi's sarcoma-associated herpesvirus (KSHV) encodes ORF57, which enhances the expression of intron-less KSHV genes on multiple post-transcriptional levels mainly affecting RNA stability and export to the cytoplasm. Yet, it remains elusive how ORF57 recognizes viral RNAs and discriminates them from cellular messenger RNAs (mRNAs). Although one common binding motif on three separate KSHV RNAs has been described, most other lytic genes lack this sequence element. In this article we will review the sequence requirements for ORF57 to enhance RNA expression and discuss a model how ORF57 achieves specificity for viral RNAs. Finally, the role of ORF57 is integrated into the viral life cycle as a complex interplay with other viral and host factors and with implications for cellular gene expression.

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“…However, subsequent studies have suggested that its predominant function may be to stabilize and promote accumulation of the RNAs [79–81]. ORF57 is now considered a multifunctional protein with roles in many RNA metabolic processes, including RNA stability, export, translation and even transcription (reviewed recently in [82–84], Figure 1). One recent addition to this body of literature is a transcriptome-wide profile of ORF57 targets using an ORF57-null virus [85].…”

Section: Post-transcriptional Control Of Viral Gene Expressionmentioning

confidence: 99%

Transcriptional and Post-Transcriptional Regulation of Viral Gene Expression in the Gamma-Herpesvirus Kaposi’s Sarcoma-Associated Herpesvirus

Butnaru

Gaglia

2018

Curr Clin Micro Rpt

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Purpose of review Kaposi’s sarcoma-associated herpesvirus (KSHV), the etiological agent of the AIDS-associated tumor Kaposi’s sarcoma, is a complex virus that expresses ~90 proteins in a regulated temporal cascade during its replication cycle. Although KSHV relies on cellular machinery for gene expression, it also uses specialized regulators to control nearly every step of the process. In this review we discuss the current understanding of KSHV gene regulation. Recent findings High-throughput sequencing and a new robust system to mutate KSHV have paved the way for comprehensive studies of KSHV gene expression, leading to the characterization of new viral factors that control late gene expression and post-transcriptional steps of gene regulation. They have also revealed key aspects of chromatin-based control of gene expression in the latent and lytic cycle. Summary The combination of mutant analysis and high-throughput sequencing will continue to expand our model of KSHV gene regulation and point to potential new targets for anti-KSHV drugs.

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Kaposi’s Sarcoma-Associated Herpesvirus ORF57 Protein: Exploiting All Stages of Viral mRNA Processing

Cited by 22 publications

References 132 publications

NP1 Protein of the Bocaparvovirus Minute Virus of Canines Controls Access to the Viral Capsid Genes via Its Role in RNA Processing

NP1 Protein of the Bocaparvovirus Minute Virus of Canines Controls Access to the Viral Capsid Genes via Its Role in RNA Processing

The KSHV RNA regulator ORF57: target specificity and its role in the viral life cycle

Transcriptional and Post-Transcriptional Regulation of Viral Gene Expression in the Gamma-Herpesvirus Kaposi’s Sarcoma-Associated Herpesvirus

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