The Pseudo-Circular Genomes of Flaviviruses: Structures, Mechanisms, and Functions of Circularization

Falco, Louis De; Silva, Nelly M.; Santos, Nuno C.; Huber, Roland G.; Martins, Ivo C.

doi:10.3390/cells10030642

Cited by 7 publications

(7 citation statements)

References 108 publications

(170 reference statements)

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“…The importance of flaviviral genome cyclization as a precursor to viral RNA replication is well-established and has been the topic of several recent reviews [ 17 , 47 ]. In brief, genome cyclization involves long-range interactions between RNA elements at the 5´ and 3´ ends of the viral genome, including the 5´-3´UAR, DAR and CS elements, which are mutually exclusive with local RNA structures in the linear genome conformation ( Figure 1 and Table 1 ).…”

Section: What Mediates the Switch From Translation To Replication In ...mentioning

confidence: 99%

The myriad roles of RNA structure in the flavivirus life cycle

Abram,

Landry,

Wang

et al. 2024

RNA Biology

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As positive-sense RNA viruses, the genomes of flaviviruses serve as the template for all stages of the viral life cycle, including translation, replication, and infectious particle production. Yet, they encode just 10 proteins, suggesting that the structure and dynamics of the viral RNA itself helps shepherd the viral genome through these stages. Herein, we highlight advances in our understanding of flavivirus RNA structural elements through the lens of their impact on the viral life cycle. We highlight how RNA structures impact translation, the switch from translation to replication, negative- and positive-strand RNA synthesis, and virion assembly. Consequently, we describe three major themes regarding the roles of RNA structure in flavivirus infections: 1) providing a layer of specificity; 2) increasing the functional capacity; and 3) providing a mechanism to support genome compaction. While the interactions described herein are specific to flaviviruses, these themes appear to extend more broadly across RNA viruses.

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Section: What Mediates the Switch From Translation To Replication In ...mentioning

confidence: 99%

The myriad roles of RNA structure in the flavivirus life cycle

Abram,

Landry,

Wang

et al. 2024

RNA Biology

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“…For the output from each algorithm, we ranked the averaged regions of the selected metric (reactivity/propensity for SHAPE/CROSS; z-score for Scanfold; entropy value for Superfold), and we selected the bottom 20% regions for each metric, thus identifying the most structured, most stable, and least ambiguous structures along the RNA of interest. Unambiguous, stable and structured regions are often encountered in known functional elements, e.g., the flavivirus 5' and 3' UTRs (21,28). We used a window of 150 nucleotides to average the different scores.…”

Section: Selecting Regions Of Structural Importancementioning

confidence: 99%

RNAvigator: A Pipeline to Identify Candidates for Functional RNA Structure Elements

Ponti

Wang²,

Wan³

et al. 2022

Front. Virol.

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Identifying structural elements in long and complex RNAs, such as long non-coding and RNA viruses, can shed light on the functionality and mechanisms of such RNAs. Here we present RNAvigator, a tool able to identify elements of structural importance by using experimental SHAPE data or SHAPE-like predictions in conjunction with stability and entropy assessments. RNAvigator recognizes regions that are the most stable, unambiguous, and structured on RNA molecules, and thus potentially functional. When relying on predictions, RNAvigator uses the CROSS algorithm, a neural network trained on experimental data that achieved an AUC of 0.74 on hepatitis C virus SHAPE-MaP data and which was able to improve the predictive power of Superfold. By using RNAvigator, we can identify known functional regions on the complete hepatitis C virus genome, including the regulatory regions CRE and IRES, and the 3’ UTR of dengue virus, a region known for the presence of structural elements essential for its replication, and functional regions of long non-coding RNAs such as XIST and HOTAIR. We envision that RNAvigator will be a useful tool for studying long and complex RNA molecules using known chemical probing data or, if they are not available, by employing predicted profiles.

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“…Although DENV and ZIKV only share about 60% of their sequence identities, many of their key structural features are conserved. These structures include elements in the 5 and 3 UTRs, which are known to be important for viral replication and translation and can pair with each other to facilitate genome circularization [63]. However, prior to the epidemic, other structural elements along the virus genome were not fully understood or studied.…”

Section: The Structurome Of Rna Viruses Involved In Pandemicsmentioning

confidence: 99%

Computational and Experimental Approaches to Study the RNA Secondary Structures of RNA Viruses

Yang

Ponti

Wan

et al. 2022

Viruses

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Most pandemics of recent decades can be traced to RNA viruses, including HIV, SARS, influenza, dengue, Zika, and SARS-CoV-2. These RNA viruses impose considerable social and economic burdens on our society, resulting in a high number of deaths and high treatment costs. As these RNA viruses utilize an RNA genome, which is important for different stages of the viral life cycle, including replication, translation, and packaging, studying how the genome folds is important to understand virus function. In this review, we summarize recent advances in computational and high-throughput RNA structure-mapping approaches and their use in understanding structures within RNA virus genomes. In particular, we focus on the genome structures of the dengue, Zika, and SARS-CoV-2 viruses due to recent significant outbreaks of these viruses around the world.

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The Pseudo-Circular Genomes of Flaviviruses: Structures, Mechanisms, and Functions of Circularization

Cited by 7 publications

References 108 publications

The myriad roles of RNA structure in the flavivirus life cycle

The myriad roles of RNA structure in the flavivirus life cycle

RNAvigator: A Pipeline to Identify Candidates for Functional RNA Structure Elements

Computational and Experimental Approaches to Study the RNA Secondary Structures of RNA Viruses

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