Rotaviral nonstructural protein 5 (NSP5) promotes proteasomal degradation of up-frameshift protein 1 (UPF1), a principal mediator of nonsense-mediated mRNA decay (NMD) pathway, to facilitate infection

Sarkar, Rakesh; Banerjee, Shreya; Mukherjee, Arpita; Chawla‐Sarkar, Mamta

doi:10.1016/j.cellsig.2021.110180

Cited by 10 publications

(12 citation statements)

References 101 publications

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“…Rotavirus is a double-stranded RNA virus displaying interplay with NMD. After entering the host cells, rotaviruses become active and produce 11 kinds of 5 capped (+) ssRNAs [59]. The key NMD factor UPF1 seems to modulate the expression of viral proteins.…”

Section: Nmd Targets Double-stranded Rna Virusesmentioning

confidence: 99%

“…The key NMD factor UPF1 seems to modulate the expression of viral proteins. The degradation kinetics of rotaviral RNAs is delayed in UPF1 and UPF2 depleted cells and UPF1 and UPF2 are associated with viral RNAs, indicating that viral RNA is sensitive to NMD, although the specific molecular mechanism of interaction between viral RNAs and UPF1 or UPF2 is not identified yet [59].…”

Section: Nmd Targets Double-stranded Rna Virusesmentioning

confidence: 99%

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Molecular Interaction of Nonsense-Mediated mRNA Decay with Viruses

Ahmed

2023

Viruses

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The virus–host interaction is dynamic and evolutionary. Viruses have to fight with hosts to establish successful infection. Eukaryotic hosts are equipped with multiple defenses against incoming viruses. One of the host defenses against viruses is the nonsense-mediated mRNA decay (NMD), an evolutionarily conserved mechanism for RNA quality control in eukaryotic cells. NMD ensures the accuracy of mRNA translation by removing the abnormal mRNAs harboring pre-matured stop codons. Many RNA viruses have a genome that contains internal stop codon(s) (iTC). Akin to the premature termination codon in aberrant RNA transcripts, the presence of iTC would activate NMD to degrade iTC-containing viral genomes. A couple of viruses have been reported to be sensitive to the NMD-mediated antiviral defense, while some viruses have evolved with specific cis-acting RNA features or trans-acting viral proteins to overcome or escape from NMD. Recently, increasing light has been shed on the NMD–virus interaction. This review summarizes the current scenario of NMD-mediated viral RNA degradation and classifies various molecular means by which viruses compromise the NMD-mediated antiviral defense for better infection in their hosts.

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Section: Nmd Targets Double-stranded Rna Virusesmentioning

confidence: 99%

Section: Nmd Targets Double-stranded Rna Virusesmentioning

confidence: 99%

Molecular Interaction of Nonsense-Mediated mRNA Decay with Viruses

Ahmed

2023

Viruses

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“…The protein encoded by UPF1 is essential for recognizing truncated transcripts and initiating the NMD process. NMD-involved proteins can also detect and degrade viral RNA, serving as an additional layer of antiviral response (Leon Sarkar et al 2022). Key genes in NMD, such as ribosomal protein (RP) genes, were also distinctly affected in their productive and unproductive isoforms by SARS-CoV-2 infection (Fig.…”

Section: Unproductive Isoform Expressionmentioning

confidence: 99%

“…4D). The rotavirus protein NSP5 also targets UPF1, leading to its proteasomal degradation and facilitating viral replication due to a burdening of the NMD pathway (Sarkar et al 2022). The porcine epidemic diarrhea virus (PEDV) reduces PABPC1 expression, while overexpression of the gene refrains viral replication (Wu et al 2022).…”

Section: Sars-cov-2 Proteins Interact With Key Antiviral Splicing And...mentioning

confidence: 99%

SARS-CoV-2 selectively induces the expression of unproductive splicing isoforms of interferon, class I MHC and splicing machinery genes

Dias

Conceição

Toledo

et al. 2023

Preprint

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Splicing is a highly conserved, intricate mechanism intimately linked to transcription elongation, serving as a pivotal regulator of gene expression. Alternative splicing may generate specific transcripts incapable of undergoing translation into proteins, designated as unproductive. A plethora of respiratory viruses, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), strategically manipulate the host’s splicing machinery to circumvent antiviral responses. During the infection, SARS-CoV-2 effectively suppresses interferon (IFN) expression, leading to B cell and CD8+ T cell leukopenia, while simultaneously increasing the presence of macrophages and neutrophils in patients with severe COVID-19. In this study, we integrated publicly available omics datasets to systematically analyze transcripts at the isoform level and delineate the nascent-peptide translatome landscapes of SARS-CoV-2-infected human cells. Our findings reveal a hitherto uncharacterized mechanism whereby SARS-CoV-2 infection induces the predominant expression of unproductive splicing isoforms in key IFN signaling genes, interferon-stimulated genes (ISGs), class I MHC genes, and splicing machinery genes, including IRF7, OAS3, HLA-B, and HNRNPH1. In stark contrast, cytokine and chemokine genes, such as IL6, CXCL8, and TNF, predominantly express productive (protein-coding) splicing isoforms in response to SARS-CoV-2 infection. We postulate that SARS-CoV-2 employs a previously unreported tactic of exploiting the host splicing machinery to bolster viral replication and subvert the immune response by selectively upregulating unproductive splicing isoforms from antigen presentation and antiviral response genes. Our study sheds new light on the molecular interplay between SARS-CoV-2 and the host immune system, offering a foundation for the development of novel therapeutic strategies to combat COVID-19.

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“…More direct involvement of ADAR1 in fostering RV replication becomes evident when depleting ADAR1 reduces RV progeny yield and overexpressing ADAR1 elevates RV titre ( Dhillon and Rao, 2018 ). Other cytosolic RNA quality control pathways such as the Staufen mediated mRNA decay (SMD) and non-sense mediated mRNA decay (NMD) are also averted by RV, possibly by disarming Staufen-1 within viroplasmic confinement and degrading UPF1, the chief effector RNA helicase involved in both SMD and NMD, by the viroplasmic protein NSP5 ( Dhillon and Rao, 2018 ; Sarkar et al., 2022 ). Unlike ADAR1, RNAi-mediated silencing of many SG/P body proteins resulted in increased viroplasmic protein (NSP2, NSP5, VP6) expressions and enhanced infectious progeny yield, indicating the antiviral importance of these host cellular determinants.…”

Section: Sequestering Host Components Within Viroplasms To Prevent Th...mentioning

confidence: 99%

Sneaking into the viral safe-houses: Implications of host components in regulating integrity and dynamics of rotaviral replication factories

Chandra

Banerjee

Saha

et al. 2022

Front. Cell. Infect. Microbiol.

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The biology of the viral life cycle essentially includes two structural and functional entities—the viral genome and protein machinery constituting the viral arsenal and an array of host cellular components which the virus closely associates with—to ensure successful perpetuation. The obligatory requirements of the virus to selectively evade specific host cellular factors while exploiting certain others have been immensely important to provide the platform for designing host-directed antiviral therapeutics. Although the spectrum of host-virus interaction is multifaceted, host factors that particularly influence viral replication have immense therapeutic importance. During lytic proliferation, viruses usually form replication factories which are specialized subcellular structures made up of viral proteins and replicating nucleic acids. These viral niches remain distinct from the rest of the cellular milieu, but they effectively allow spatial proximity to selective host determinants. Here, we will focus on the interaction between the replication compartments of a double stranded RNA virus rotavirus (RV) and the host cellular determinants of infection. RV, a diarrheagenic virus infecting young animals and children, forms replication bodies termed viroplasms within the host cell cytoplasm. Importantly, viroplasms also serve as the site for transcription and early morphogenesis of RVs and are very dynamic in nature. Despite advances in the understanding of RV components that constitute the viroplasmic architecture, knowledge of the contribution of host determinants to viroplasm dynamicity has remained limited. Emerging evidence suggests that selective host determinants are sequestered inside or translocated adjacent to the RV viroplasms. Functional implications of such host cellular reprogramming are also ramifying—disarming the antiviral host determinants and usurping the pro-viral components to facilitate specific stages of the viral life cycle. Here, we will provide a critical update on the wide variety of host cellular pathways that have been reported to regulate the spatial and temporal dynamicity of RV viroplasms. We will also discuss the methods used so far to study the host-viroplasm interactions and emphasize on the potential host factors which can be targeted for therapeutic intervention in the future.

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Rotaviral nonstructural protein 5 (NSP5) promotes proteasomal degradation of up-frameshift protein 1 (UPF1), a principal mediator of nonsense-mediated mRNA decay (NMD) pathway, to facilitate infection

Cited by 10 publications

References 101 publications

Molecular Interaction of Nonsense-Mediated mRNA Decay with Viruses

Molecular Interaction of Nonsense-Mediated mRNA Decay with Viruses

SARS-CoV-2 selectively induces the expression of unproductive splicing isoforms of interferon, class I MHC and splicing machinery genes

Sneaking into the viral safe-houses: Implications of host components in regulating integrity and dynamics of rotaviral replication factories

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