cis-Acting signals that promote genome replication in rotavirus mRNA

Patton, John T.; Wentz, Melissa J.; Xiaobo, Jiang; Ramig, Robert F.

doi:10.1128/jvi.70.6.3961-3971.1996

Cited by 66 publications

(68 citation statements)

References 49 publications

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“…Similar studies to identify cis-acting signals regulating replication of rotavirus RNA have been carried out using SA11 genome segment 8 (SA11-8) templates (23). These studies also identified a tripartite cis-acting replication signal.…”

Section: Discussionmentioning

confidence: 70%

The 3'-terminal consensus sequence of rotavirus mRNA is the minimal promoter of negative-strand RNA synthesis

Wentz

Patton

Ramig

1996

J Virol

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We used an in vitro template-dependent replicase assay (D. Chen, C. Zeng, M. Wentz, M. Gorziglia, M. Estes, and R. Ramig. J. Virol. 68:7030-7039, 1994) to identify the cis-acting signals required for replication of a genome segment 9 template from the group A rotavirus strain OSU. The replicase phenotypes for a panel of templates with internal deletions or 3-terminal truncations indicated that no essential replication signals were present within the open reading frame and that key elements were present in the 5 and 3 noncoding regions. Chimeric constructs containing portions of viral sequence ligated to a nonviral backbone were generated to further map the regions required for in vitro replication of segment 9. The data from these constructs showed that the 3-terminal seven nucleotides of the segment 9 mRNA provided the minimum requirement for replication (minimal promoter). Analysis of additional chimeric templates demonstrated that sequences capable of enhancing replication from the minimal promoter were located immediately upstream of the minimal promoter and at the extreme 5 terminus of the template. Mutational analysis of the minimal promoter revealed that the 3-terminal -CC residues are required for efficient replication. Comparison of the replication levels for templates with guanosines and uridines at nucleotides ؊4 to ؊6 from the 3 terminus compared with levels for templates containing neither of these residues at these positions indicated that either or both residues must be present in this region for efficient replication in vitro.

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Section: Discussionmentioning

confidence: 70%

The 3'-terminal consensus sequence of rotavirus mRNA is the minimal promoter of negative-strand RNA synthesis

Wentz

Patton

Ramig

1996

J Virol

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“…These panhandle RNA structures are required for viral RNA transcription and replication (30,51,52). Finally, rotaviruses appear to utilize complementarity at the termini of their viral RNA template to mediate negative-strand RNA synthesis (35,50). Thus, the 5Ј and 3Ј termini of various viral RNA molecules exhibit a predilection for proximal orientations, and these proximal RNA termini seem to facilitate the regulation of viral gene expression and replication.…”

Section: Discussionmentioning

confidence: 99%

Poliovirus 5′-Terminal Cloverleaf RNA Is Required in cis for VPg Uridylylation and the Initiation of Negative-Strand RNA Synthesis

Lyons¹,

Murray²,

Roberts³

et al. 2001

J Virol

108

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Chimeric poliovirus RNAs, possessing the 5 nontranslated region (NTR) of hepatitis C virus in place of the 5 NTR of poliovirus, were used to examine the role of the poliovirus 5 NTR in viral replication. The chimeric viral RNAs were incubated in cell-free reaction mixtures capable of supporting the sequential translation and replication of poliovirus RNA. Using preinitiation RNA replication complexes formed in these reactions, we demonstrated that the 3 NTR of poliovirus RNA was insufficient, by itself, to recruit the viral replication proteins required for negative-strand RNA synthesis. The 5-terminal cloverleaf of poliovirus RNA was required in cis to form functional preinitiation RNA replication complexes capable of uridylylating VPg and initiating the synthesis of negative-strand RNA. These results are consistent with a model in which the 5-terminal cloverleaf and 3 NTRs of poliovirus RNA interact via temporally dynamic ribonucleoprotein complexes to coordinately mediate and regulate the sequential translation and replication of poliovirus RNA.The single-stranded positive-sense RNA genome of poliovirus functions sequentially as an mRNA for viral protein synthesis and then as a template for viral negative-strand RNA synthesis (33). Cytoplasmic extracts from HeLa cells support the sequential translation and replication of poliovirus RNA (5, 31). In the presence of 2 mM guanidine HCl, cell-free translation-replication reactions support the translation of viral RNA and the accumulation of viral preinitiation RNA replication complexes (4, 6). Guanidine HCl reversibly blocks the initiation of negative-strand RNA synthesis by interfering with the function of viral protein 2CATPase (3,38,40). When preinitiation RNA replication complexes are resuspended in reaction mixtures in the absence of guanidine HCl, the preinitiation RNA replication complexes synchronously initiate the synthesis of viral negative-strand RNA (6). Ribosomes translating the viral mRNA within preinitiation RNA replication complexes prevent the synthesis of negative-strand RNA (8,15). Thus, the conversion of viral ribonucleoprotein complexes into preinitiation RNA replication complexes is an important temporally regulated event in the replication of poliovirus RNA.Contemporary models of eukaryotic mRNA translation suggest that the 5Ј and 3Ј nontranslated regions (NTRs) of mRNAs communicate via RNA binding proteins bound to both termini of the mRNA (14,19,42). In particular, poly(A) binding protein bound to 3Ј-terminal poly(A) interacts with eukaryotic initiation factors eIF4G I and II anchored to the 5Ј NTR of mRNA, bringing the 5Ј and 3Ј NTRs into proximity (49). During the course of a poliovirus infection, viral protein 2APro mediates the cleavage of eIF4G I and II and poly(A) binding proteins (11,18,23,24). This leads to the shutoff of cap-dependent host protein synthesis and precludes the ability of eIF4G I and II and poly(A) binding protein to form proteinprotein bridges between the 5Ј and 3Ј termini of mRNAs, including poliovirus RNA. Therefo...

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“…This relationship between transcription and replication is being understood in greater detail from studies conducted using cystovirus ~6 Van Dijk et al, 1995;Qiao et al, 1997;Mindich, 1999), where a complete viral reconstitution system is available to allow recovery of infectious virions from mRNA transcripts or cDNA clones of the viral genome (Olkkonen et al, 1990). Although no reconstitution system is yet available for any of the reoviruses, studies conducted using baculovirusexpressed recombinant rotavirus-like particles containing the viral RNA polymerase coexpressed with the inner capsid protein have begun to clarify the mechanism by which the dsRNA genome is synthesized from the mRNA templates in rotavirus Patton et al, 1996;Zeng et al, 1996).…”

Section: Mature Mrna Transcriptsmentioning

confidence: 99%

Mechanism of genome transcription in segmented dsRNA viruses

Lawton

Estes

Prasad

2000

Advances in Virus Research

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Genome transcription is a critical stage in the life cycle of a virus, as this is the process by which the viral genetic information is presented to the host cell protein synthesis machinery for the production of the viral proteins needed for genome replication and progeny virion assembly. Viruses with dsRNA genomes face a particular challenge in that host cells do not produce proteins which can transcribe from a dsRNA template. Therefore, dsRNA viruses contain all of the necessary enzymatic machinery to synthesize complete mRNA transcripts within the core without the need for disassembly. Indeed one of the more striking observations about genome transcription in dsRNA viruses is that this process occurs efficiently only when the transcriptionally competent particle is fully intact. This observation suggests that all of the components of the TCP, including the viral genome, the transcription enzymes, and the viral capsid, function together to produce and release mRNA transcripts and that each component has a specific and critical role to play in promoting the efficiency of this process. This review has examined the process of genome transcription in dsRNA viruses from the perspective of rotavirus as a model system. However, despite numerous architectural and organizational differences among the families of dsRNA viruses, numerous studies suggest that the basic mechanism of mRNA production may be similar in most, if not all, viruses having dsRNA genomes. Important functional similarities include (1) the presence of a capsid-bound RNA-dependent RNA polymerase, which produces single-stranded mRNA transcripts from the dsRNA genome and regenerates the dsRNA genome from single-stranded RNA templates; (2) in viruses infecting eukaryotic hosts, the presence of all the enzymatic activities needed to generate the 5' cap required by the eukaryotic translation machinery; (3) the high degree of structural order present in the packaged genome, suggesting the requirement for organization in the viral core; (4) the role of the innermost capsid protein as a scaffold on which the core components of the transcription apparatus are assembled; and (5) the release of nascent mRNA transcripts through channels at the icosahedral vertices. The process of genome transcription in dsRNA viruses will become better understood as structural studies progress to higher resolution and as more viruses become amenable to study using site-directed mutagenesis coupled with viral reconstitution to generate recombinant particles having precise functional and structural changes. Future studies will dissect important intermolecular interactions required for efficient mRNA synthesis and will shed further light on the reasons for which the viral core must be structurally intact in order for transcription to occur efficiently. Structural studies of the capping enzymes at atomic resolution will reveal how multiple enzyme activities reside within a single polypeptide and how they act in concert to synthesize the 5' cap on the end of each mature transcript. Pe...

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cis-Acting signals that promote genome replication in rotavirus mRNA

Cited by 66 publications

References 49 publications

The 3'-terminal consensus sequence of rotavirus mRNA is the minimal promoter of negative-strand RNA synthesis

The 3'-terminal consensus sequence of rotavirus mRNA is the minimal promoter of negative-strand RNA synthesis

Poliovirus 5′-Terminal Cloverleaf RNA Is Required in cis for VPg Uridylylation and the Initiation of Negative-Strand RNA Synthesis

Mechanism of genome transcription in segmented dsRNA viruses

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