Single-molecule portrait of DNA and RNA double helices

Arias-González, J. Ricardo

doi:10.1039/c4ib00163j

Cited by 34 publications

(37 citation statements)

References 218 publications

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“…The filaments had a uniform average diameter of 2.68 nm (SD = 0.23 nm, n = 80 from two tomograms) ( Fig. 1f), which corresponds well to the diameter of the A-form RNA double-stranded helix 19 and is in accord with anti-dsRNA immuno-EM SARS-CoV-1 studies 10 . We regularly observed filament branching points (Fig.…”

Section: Resultssupporting

confidence: 68%

SARS-CoV-2 structure and replication characterized by in situ cryo-electron tomography

et al. 2020

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the COVID19 pandemic, is a highly pathogenic β-coronavirus. As other coronaviruses, SARS-CoV-2 is enveloped, replicates in the cytoplasm and assembles at intracellular membranes. Here, we structurally characterize the viral replication compartment and report critical insights into the budding mechanism of the virus, and the structure of extracellular virions close to their native state by in situ cryo-electron tomography and subtomogram averaging. We directly visualize RNA filaments inside the double membrane vesicles, compartments associated with viral replication. The RNA filaments show a diameter consistent with double-stranded RNA and frequent branching likely representing RNA secondary structures. We report that assembled S trimers in lumenal cisternae do not alone induce membrane bending but laterally reorganize on the envelope during virion assembly. The viral ribonucleoprotein complexes (vRNPs) are accumulated at the curved membrane characteristic for budding sites suggesting that vRNP recruitment is enhanced by membrane curvature. Subtomogram averaging shows that vRNPs are distinct cylindrical assemblies. We propose that the genome is packaged around multiple separate vRNP complexes, thereby allowing incorporation of the unusually large coronavirus genome into the virion while maintaining high steric flexibility between the vRNPs.

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Section: Resultssupporting

confidence: 68%

SARS-CoV-2 structure and replication characterized by in situ cryo-electron tomography

et al. 2020

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“…These structures are flexible platforms that interact with proteins, these interactions being at the core of information processing in cells. 18 Understanding genetic information storage and transfer is not only interesting from a biological point of view but also inspiring nanotechnologies for recognition and for information and communication. 11,12 We next illustrate the above theory with two natural processes in which information and thermodynamics appear together: DNA replication and RNA transcription.…”

Section: Genetic Information Transfermentioning

confidence: 99%

Thermodynamic framework for information in nanoscale systems with memory

Arias-González

2017

The Journal of Chemical Physics

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Information is represented by linear strings of symbols with memory that carry errors as a result of their stochastic nature. Proofreading and edition are assumed to improve certainty although such processes may not be effective. Here, we develop a thermodynamic theory for material chains made up of nanoscopic subunits with symbolic meaning in the presence of memory. This framework is based on the characterization of single sequences of symbols constructed under a protocol and is used to derive the behavior of ensembles of sequences similarly constructed. We then analyze the role of proofreading and edition in the presence of memory finding conditions to make revision an effective process, namely, to decrease the entropy of the chain. Finally, we apply our formalism to DNA replication and RNA transcription finding that Watson and Crick hybridization energies with which nucleotides are branched to the template strand during the copying process are optimal to regulate the fidelity in proofreading. These results are important in applications of information theory to a variety of solid-state physical systems and other biomolecular processes.

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“…G-Quadruplexes (G4) are non-canonical conformations of DNA or RNA sequences rich in guanine nucleobases. Unlike the classic double helix 1 , the basic structural unit in the G4 motif is the G-tetrad , a planar arrangement of four guanines (G) nucleobases held by Hoogsten hydrogen bonds 2 . The presence of monovalent cations like K + and Na + stabilises the highly electronegative central channel along the axis of the G4 stem.…”

Section: Introductionmentioning

confidence: 99%

Mesoscopic model for DNA G-quadruplex unfolding

Bergues-Pupo

Gutiérrez

Arias-González

et al. 2017

Sci Rep

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Genomes contain rare guanine-rich sequences capable of assembling into four-stranded helical structures, termed G-quadruplexes, with potential roles in gene regulation and chromosome stability. Their mechanical unfolding has only been reported to date by all-atom simulations, which cannot dissect the major physical interactions responsible for their cohesion. Here, we propose a mesoscopic model to describe both the mechanical and thermal stability of DNA G-quadruplexes, where each nucleotide of the structure, as well as each central cation located at the inner channel, is mapped onto a single bead. In this framework we are able to simulate loading rates similar to the experimental ones, which are not reachable in simulations with atomistic resolution. In this regard, we present single-molecule force-induced unfolding experiments by a high-resolution optical tweezers on a DNA telomeric sequence capable of adopting a G-quadruplex conformation. Fitting the parameters of the model to the experiments we find a correct prediction of the rupture-force kinetics and a good agreement with previous near equilibrium measurements. Since G-quadruplex unfolding dynamics is halfway in complexity between secondary nucleic acids and tertiary protein structures, our model entails a nanoscale paradigm for non-equilibrium processes in the cell.

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Single-molecule portrait of DNA and RNA double helices

Cited by 34 publications

References 218 publications

SARS-CoV-2 structure and replication characterized by in situ cryo-electron tomography

SARS-CoV-2 structure and replication characterized by in situ cryo-electron tomography

Thermodynamic framework for information in nanoscale systems with memory

Mesoscopic model for DNA G-quadruplex unfolding

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