Conformational organization of the 3′ untranslated region in the tomato bushy stunt virus genome

Hong, Na; Fabian, Marc R.; White, K. Andrew

doi:10.1261/rna.238606

Cited by 24 publications

(26 citation statements)

References 32 publications

(72 reference statements)

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“…In the TBSV genome, two different functional RNA-RNA interactions involving sequences in internal or terminal loops have been described previously (43). These respective interactions operate to modulate TBSV genome replication (4,18,19,26) or facilitate efficient cap-independent translation of viral proteins (5,6). Considering these cases, it is not surprising to find that similar examples related to sg mRNA transcription also exist.…”

Section: Discussionmentioning

confidence: 94%

A Multicomponent RNA-Based Control System Regulates Subgenomic mRNA Transcription in a Tombusvirus

Lin

White

2007

J Virol

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During infections, positive-strand RNA tombusviruses transcribe two subgenomic (sg) mRNAs that allow for the expression of a subset of their genes. This process is thought to involve an unconventional mechanism involving the premature termination of the virally encoded RNA-dependent RNA polymerase while it is copying the virus genome. The 3 truncated minus strands generated by termination are then used as templates for sg mRNA transcription. In addition to requiring an extensive network of long-distance RNA-RNA interactions (H.-X. Lin and K. A. White, EMBO J. 23:3365-3374, 2004), the transcription of tombusvirus sg mRNAs also involves several additional RNA structures. In vivo analysis of these diverse RNA elements revealed that they function at distinct steps in the process by facilitating the formation or stabilization of the long-distance interactions, modulating minus-strand template production, or promoting the initiation of sg mRNA transcription. All of the RNA elements characterized could be readily incorporated into a premature termination model for sg mRNA transcription. Overall, the analyses revealed a complex system that displays a high level of structural integration and functional coordination. This multicomponent RNA-based control system may serve as a useful paradigm for understanding related transcriptional processes in other positive-sense RNA viruses.Most positive-strand RNA genomes that are polycistronic rely on the transcription of smaller genome-derived mRNAs, termed subgenomic (sg) mRNAs, to mediate the translation of their 3Ј proximally positioned genes (17). Although these viruses use different mechanisms to produce sg mRNAs, the involvement of their virally encoded RNA-dependent RNA polymerase (RdRp) is common to all (1). In viruses such as Brome mosaic virus, sg mRNAs are generated by the internal initiation of transcription by the RdRp on full-length negative strands of the viral genomes (16). Alternatively, corona-and arteriviruses transcribe their sg mRNAs from noncontiguous, minus-strand RNA templates that are produced by discontinuous RdRp copying of their genomes (10,24,25,30,36,38). A third mechanism, suggested by studies of Red clover necrotic mosaic virus (RCNMV), involves the premature termination (PT) of the RdRp while copying viral RNA genomes and the subsequent use of the 3Ј truncated minus strands as templates for sg mRNA transcription (33). This PT mechanism has also been proposed to function in a variety of viruses (e.g., Torovirus, Nodavirus, Closterovirus, and Tombusvirus) (7,14,27,35,39,41,48). Despite its prevalence and importance, many mechanistic aspects of PT-based sg mRNA transcription are poorly understood and comprehensive functional models that include all of the cis-and trans-acting factors involved are lacking (41).Tombusviruses represent one of the most advanced systems for studying viral RNA synthesis and gene expression (43). The prototype of this genus, Tomato bushy stunt virus (TBSV), possesses a small, 4.8-kb, positive-strand RNA genome that carries fi...

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Section: Discussionmentioning

confidence: 94%

A Multicomponent RNA-Based Control System Regulates Subgenomic mRNA Transcription in a Tombusvirus

Lin

White

2007

J Virol

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“…For example, long-range interactions between the 5′-end and 3′-end to circularize gRNA are required for replication of positive-strand plant RNA viruses, 55–61 as well as animal RNA viruses. 62–68 Interactions between the UTR and coding region have also been reported to modulate viral replication.…”

Section: Discussionmentioning

confidence: 99%

Nuclear Magnetic Resonance Study of RNA Structures at the 3′-End of the Hepatitis C Virus Genome

et al. 2017

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The 3′-end of the genomic RNA of the hepatitis C virus (HCV) embeds conserved elements that regulate viral RNA synthesis and protein translation by mechanisms that have yet to be elucidated. Previous studies with oligo-RNA fragments have led to multiple, mutually exclusive secondary structure predictions, indicating that HCV RNA structure may be context-dependent. Here we employed a nuclear magnetic resonance (NMR) approach that involves long-range adenosine interaction detection, coupled with site-specific 2H labeling, to probe the structure of the intact 3′-end of the HCV genome (385 nucleotides). Our data reveal that the 3′-end exists as an equilibrium mixture of two conformations: an open conformation in which the 98 nucleotides of the 3′-tail (3′X) form a two-stem–loop structure with the kissing-loop residues sequestered and a closed conformation in which the 3′X rearranges its structure and forms a long-range kissing-loop interaction with an upstream cis-acting element 5BSL3.2. The long-range kissing species is favored under high-Mg2+ conditions, and the intervening sequences do not affect the equilibrium as their secondary structures remain unchanged. The open and closed conformations are consistent with the reported function regulation of viral RNA synthesis and protein translation, respectively. Our NMR detection of these RNA conformations and the structural equilibrium in the 3′-end of the HCV genome support its roles in coordinating various steps of HCV replication.

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“…For instance, the 3′-terminal part of the TBSV genome contains four RNA elements important for replication (Fabian et al, 2003;Na et al, 2006) which, together with the 3′ UTR sequences of carmoviruses, are described in detail in Box 6.6. For instance, the 3′-terminal part of the TBSV genome contains four RNA elements important for replication (Fabian et al, 2003;Na et al, 2006) which, together with the 3′ UTR sequences of carmoviruses, are described in detail in Box 6.6.…”

Section: Box 73 Alfalfa Mosaic Virus Cp Involvement In Translation Amentioning

confidence: 99%

Replication of Plant Viruses

Hull

2014

Plant Virology

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Conformational organization of the 3′ untranslated region in the tomato bushy stunt virus genome

Cited by 24 publications

References 32 publications

A Multicomponent RNA-Based Control System Regulates Subgenomic mRNA Transcription in a Tombusvirus

A Multicomponent RNA-Based Control System Regulates Subgenomic mRNA Transcription in a Tombusvirus

Nuclear Magnetic Resonance Study of RNA Structures at the 3′-End of the Hepatitis C Virus Genome

Replication of Plant Viruses

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