Physical and Functional Analysis of Viral RNA Genomes by SHAPE

Boerneke, Mark A.; Ehrhardt, Jeffrey E; Weeks, Kevin M.

doi:10.1146/annurev-virology-092917-043315

Cited by 64 publications

(49 citation statements)

References 119 publications

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“…RNA viruses encode the information needed to take control of the host cell on two levels (Boerneke et al, 2019). On one hand, the linear sequence of their RNA genomes encodes for all the proteins needed to take over the host cell machinery and to assemble new viral particles.…”

Section: Introductionmentioning

confidence: 99%

“…As a consequence of their high mutation rates, RNA viruses can rapidly develop resistance towards drugs and vaccines by slightly altering their core proteins (Irwin et al, 2016). In contrast, certain RNA structures formed in the context of viral RNA genomes are well conserved (Boerneke et al, 2019), in spite of changes in the underlying encoded amino acid sequence, making them valuable therapeutic targets.…”

Section: Introductionmentioning

confidence: 99%

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Genome-wide mapping of therapeutically-relevant SARS-CoV-2 RNA structures

Manfredonia

Nithin

Ponce-Salvatierra

et al. 2020

Preprint

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SARS-CoV-2 is a betacoronavirus with a linear single-stranded, positive-sense RNA genome of ~30 kb, whose outbreak caused the still ongoing COVID-19 pandemic. The ability of coronaviruses to rapidly evolve, adapt, and cross species barriers makes the development of effective and durable therapeutic strategies a challenging and urgent need. As for other RNA viruses, genomic RNA structures are expected to play crucial roles in several steps of the coronavirus replication cycle. Despite this, only a handful of functionally conserved structural elements within coronavirus RNA genomes have been identified to date.Here, we performed RNA structure probing by SHAPE-MaP to obtain a single-base resolution secondary structure map of the full SARS-CoV-2 coronavirus genome. The SHAPE-MaP probing data recapitulate the previously described coronavirus RNA elements (5′ UTR, ribosomal frameshifting element, and 3′ UTR), and reveal new structures. Secondary structure-restrained 3D modeling of highly-structured regions across the SARS-CoV-2 genome allowed for the identification of several putative druggable pockets. Furthermore, ~8% of the identified structure elements show significant covariation among SARS-CoV-2 and other coronaviruses, hinting at their functionally-conserved role. In addition, we identify a set of persistently single-stranded regions having high sequence conservation, suitable for the development of antisense oligonucleotide therapeutics.Collectively, our work lays the foundation for the development of innovative RNA-targeted therapeutic strategies to fight SARS-related infections.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Genome-wide mapping of therapeutically-relevant SARS-CoV-2 RNA structures

Manfredonia

Nithin

Ponce-Salvatierra

et al. 2020

Preprint

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“…In tombusviruses, this initiation site is positioned just downstream from the transcription-promoting AS1/RS1 interaction ( Supplementary Figure S1 ), which forms the closing stem of the RNA domain LD2, as shown for TBSV (Figure 1B) ( 48 , 49 ). Corresponding structure probing analysis ( 63 ) of the CIRV genome predicted a comparable AS1/RS1-containing LD2 (Figure 2D and Supplementary Figure S2A ) that structurally mimicked that in TBSV ( Supplementary Figure S2B ). Also, the CIRV AS1/RS1 LDRI was shown, as demonstrated previously for TBSV ( 49 ), to be necessary for sg mRNA1 transcription ( Supplementary Figure S3 ).…”

Section: Resultsmentioning

confidence: 95%

Activation of viral transcription by stepwise largescale folding of an RNA virus genome

Chkuaseli

White

2020

Nucleic Acids Research

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The genomes of RNA viruses contain regulatory elements of varying complexity. Many plus-strand RNA viruses employ largescale intra-genomic RNA-RNA interactions as a means to control viral processes. Here, we describe an elaborate RNA structure formed by multiple distant regions in a tombusvirus genome that activates transcription of a viral subgenomic mRNA. The initial step in assembly of this intramolecular RNA complex involves the folding of a large viral RNA domain, which generates a discontinuous binding pocket. Next, a distally-located protracted stem-loop RNA structure docks, via base-pairing, into the binding site and acts as a linchpin that stabilizes the RNA complex and activates transcription. A multi-step RNA folding pathway is proposed in which rate-limiting steps contribute to a delay in transcription of the capsid protein-encoding viral subgenomic mRNA. This study provides an exceptional example of the complexity of genome-scale viral regulation and offers new insights into the assembly schemes utilized by large intra-genomic RNA structures.

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“…Whereas DNA has been selected as a for genetic information storage, RNA is used for transporting the genetic information outside the cell nucleus, in the form of messenger RNA and to take part to the biochemical pathways involved in the gene expression. According to some theories about the origin of life, RNA molecules are thought to both store information for simpler biological systems, [98] and act as a catalyst (for instance the ribosome is composed primarily of RNA). [99]- [100] On the printing point of view, DNA is among the most suitable molecular systems for building up artificial nano-to microstructures featuring complexity and programmability, based upon the specific Watson-Crick base pairings, leading to the definition of the field of DNA nanotechnology.…”

Section: Nucleic Acidsmentioning

confidence: 99%

Artificial Biosystems by Printing Biology

Arrabito

Ferrara

Bonasera

et al. 2020

Small

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The continuous progress of printing technologies over the past 20 years has fueled the development of a wide plethora of applications in materials sciences, flexible electronics and biotechnologies. More recently, printing methodologies have started up to explore the world of Artificial Biology, offering new paradigms in the direct assembly of Artificial Biosystems (small condensates, compartments, networks, tissues and organs) by mimicking the result of the evolution of living systems and also by redesigning natural biological systems, taking inspiration from them. This recent progress is reported in terms of a new field here defined as Printing Biology, resulting from the intersection between the field of printing and the bottom up Synthetic Biology. Printing Biology explores new approaches for the reconfigurable assembly of designed lifelike or life-inspired structures. This review presents this emerging field, highlighting its main features, i.e. printing methodologies (from 2D to 3D), molecular ink properties, deposition mechanisms, and finally the applications and future challenges. Printing Biology is expected to show a growing impact on the development of biotechnology and lifeinspired fabrication. Printing Biology employs different technologies dispensing molecular inks with tunable composition (molecules, polymers, biomolecules) and drop sizes (from nano-up to macroscale) onto solids or into liquids to develop lifelike or life-inspired artificial biosystems (from small condensates, to compartments up to networks, tissues and organs). This work reviews the extraordinary potential of this emerging research field.

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Physical and Functional Analysis of Viral RNA Genomes by SHAPE

Cited by 64 publications

References 119 publications

Genome-wide mapping of therapeutically-relevant SARS-CoV-2 RNA structures

Genome-wide mapping of therapeutically-relevant SARS-CoV-2 RNA structures

Activation of viral transcription by stepwise largescale folding of an RNA virus genome

Artificial Biosystems by Printing Biology

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