La, PTB, and PAB proteins bind to the 3′ untranslated region of Norwalk virus genomic RNA

Gutiérrez-Escolano, Ana Lorena; Vázquez-Ochoa, Melina; Escobar-Herrera, Jaime; Hernández-Acosta, Javier

doi:10.1016/j.bbrc.2003.10.066

Cited by 44 publications

(58 citation statements)

References 29 publications

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“…La interacts with the 5= and 3= ends of the Japanese encephalitis virus genome (69,70) and contributes to the translation of a subset of cellular mRNAs known as TOP mRNAs (41). We identified La protein in purifications prepared using either the 5= or 3= extremities of the MNV genomic RNA (Table 1); these proteins have also been reported for Norwalk virus (25,27), further confirming the utility of MNV as a model for studying aspects of human norovirus biology. La immunoprecipitation demonstrated an association, either direct or indirect, with the viral replication complex (Fig.…”

Section: Figsupporting

confidence: 64%

“…While to date there has been limited information regarding the role of host nucleic acid-binding proteins in the norovirus life cycle, previous studies demonstrated that a number of host factors interact with the Norwalk virus genome. Specifically, La, PTB, and PABP interact with the 3= untranslated region (UTR) of the Norwalk virus genome (27), and La, PTB, PCBP-2, and hnRNPL interact with the 5= end (25). While a functional role for these interactions is yet to be determined, due to the lack of an amenable functional assay, studies have indicated that cellular proteins may contribute to genome circularization via interactions with the 5= and 3= extremities of the viral genome (60).…”

Section: Figmentioning

confidence: 99%

“…Previous reports have illustrated that one of the nonstructural proteins from the prototype human norovirus Norwalk virus interacts with components of the vacuolar sorting pathway and alters host cell secretion (16,63). Studies have also identified a number of host cell nucleic acid binding proteins that interact with the 5= and 3= extremities of the human norovirus genomic RNA (25,27). While a definitive function of these interactions has yet to be confirmed due to lack of suitable experimental systems, it is likely they contribute to genome circularization (60).…”

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confidence: 99%

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Identification of RNA-Protein Interaction Networks Involved in the Norovirus Life Cycle

Vashist

Ureña

Chaudhry

et al. 2012

J Virol

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Human noroviruses are one of the major causes of acute gastroenteritis in the developed world, yet our understanding of their molecular mechanisms of genome translation and replication lags behind that for many RNA viruses. Due to the nonculturable nature of human noroviruses, many related members of the Caliciviridae family of small RNA viruses are often used as model systems to dissect the finer details of the norovirus life cycle. Murine norovirus (MNV) has provided one such system with which to study the basic mechanisms of norovirus translation and replication in cell culture. In this report we describe the use of riboproteomics to identify host factors that interact with the extremities of the MNV genome. This network of RNA-protein interactions contains many well-characterized host factors, including PTB, La, and DDX3, which have been shown to play a role in the life cycle of other RNA viruses. By using RNA coimmunoprecipitation, we confirmed that a number of the factors identified using riboproteomics are associated with the viral RNA during virus replication in cell culture. We further demonstrated that RNA inhibition-mediated knockdown of the intracellular levels of a number of these factors inhibits or slows norovirus replication in cell culture, allowing identification of new intracellular targets for this important group of pathogens. The genomes of small positive-strand RNA viruses must not only encode the viral proteins required for viral genome replication and infectious virus production, but they must also contain cis-acting RNA sequences and structures that play critical roles in the virus life cycle (40). Host cell factors that interact with these RNA elements play important roles in all aspects of the virus life cycle (49); consequently, the manipulation of these interactions via the introduction of mutations into the viral genome is a viable approach to rational attenuation (24,26,57,78). In addition, the modification of these RNA-protein interactions by using small-molecule or peptide inhibitors has been shown to provide antiviral activity, at least in cell culture (8,19).Noroviruses, first identified in 1972 by Albert Kapikian (33), are now accepted as the major cause of viral gastroenteritis in the developed world (21). Reports indicate that in excess of 23 million cases occur each year in the United States, resulting in a significant economic impact. Now over 20 years since the first full genome sequence of a norovirus became available (77), investigators are still unable to efficiently propagate human noroviruses in cell culture (15, 37). Recent data have indicated that the viral RNA purified from the feces of individuals infected with Norwalk virus, the prototype human norovirus, can replicate when transfected into immortalized cells in culture (23). These data clearly demonstrate that one of the major blocks in the ability of human noroviruses to replicate in cell culture is the ability of the virus to enter and spread from cell to cell. It is also clear that the intracellular environ...

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Section: Figsupporting

confidence: 64%

Section: Figmentioning

confidence: 99%

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confidence: 99%

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Identification of RNA-Protein Interaction Networks Involved in the Norovirus Life Cycle

Vashist

Ureña

Chaudhry

et al. 2012

J Virol

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“…Other candidates that might interact with PTB are the cold shock domain (CSD) containing protein, which was found in complex with PTB on vascular endothelial growth factor mRNA (Coles et al, 2004) and PSH, p54(nrb) and U1A, which bind together with PTB to the COX-2 3'-UTR (Hall-Pogar et al, 2007). In addition, it has been observed that PTB bind together with La to the 3'-UTR of the Norwalk virus RNA (Gutiérrez-Escolano et al, 2003). It is therefore likely that the cooperate binding of PTB and various other RNA-binding proteins results in stabilization of the mRNAs.…”

Section: Ptb Co-operativety With Other Mrna-binding Proteinsmentioning

confidence: 99%

The importance of RNA binding proteins in preproinsulin mRNA stability

Fred

Welsh²

2009

Molecular and Cellular Endocrinology

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“…The 5=-end sequence of both the genomic and subgenomic RNAs is highly conserved among several members of the family Caliciviridae (14,15). Moreover, their 5=-and 3=-end regions contain several conserved RNA secondary structures, with various sizes and positions, implicated in viral replication (16)(17)(18), as well as viral pathogenesis (14).…”

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confidence: 99%

Norovirus Genome Circularization and Efficient Replication Are Facilitated by Binding of PCBP2 and hnRNP A1

López-Manríquez

Vashist

Ureña

et al. 2013

J Virol

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c Sequences and structures within the terminal genomic regions of plus-strand RNA viruses are targets for the binding of host proteins that modulate functions such as translation, RNA replication, and encapsidation. Using murine norovirus 1 (MNV-1), we describe the presence of long-range RNA-RNA interactions that were stabilized by cellular proteins. The proteins potentially responsible for the stabilization were selected based on their ability to bind the MNV-1 genome and/or having been reported to be involved in the stabilization of RNA-RNA interactions. Cell extracts were preincubated with antibodies against the selected proteins and used for coprecipitation reactions. Extracts treated with antibodies to poly(C) binding protein 2 (PCBP2) and heterogeneous nuclear ribonucleoprotein (hnRNP) A1 significantly reduced the 5=-3= interaction. Both PCBP2 and hnRNP A1 recombinant proteins stabilized the 5=-3= interactions and formed ribonucleoprotein complexes with the 5= and 3= ends of the MNV-1 genomic RNA. Mutations within the 3= complementary sequences (CS) that disrupt the 5=-3=-end interactions resulted in a significant reduction of the viral titer, suggesting that the integrity of the 3=-end sequence and/or the lack of complementarity with the 5= end is important for efficient virus replication. Small interfering RNA-mediated knockdown of PCBP2 or hnRNP A1 resulted in a reduction in virus yield, confirming a role for the observed interactions in efficient viral replication. PCBP2 and hnRNP A1 induced the circularization of MNV-1 RNA, as revealed by electron microscopy. This study provides evidence that PCBP2 and hnRNP A1 bind to the 5= and 3= ends of the MNV-1 viral RNA and contribute to RNA circularization, playing a role in the virus life cycle.

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La, PTB, and PAB proteins bind to the 3′ untranslated region of Norwalk virus genomic RNA

Cited by 44 publications

References 29 publications

Identification of RNA-Protein Interaction Networks Involved in the Norovirus Life Cycle

Identification of RNA-Protein Interaction Networks Involved in the Norovirus Life Cycle

The importance of RNA binding proteins in preproinsulin mRNA stability

Norovirus Genome Circularization and Efficient Replication Are Facilitated by Binding of PCBP2 and hnRNP A1

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