ArticleProceedings of the National Academy of Sciences of the United States of America2014
Structural insights into the effects of 2'-5' linkages on the RNA duplex.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed.
- Acyclic serinol nucleic acid modification of siRNAs overcomes seed region mediated off-target effects while maintaining potency.Nucleic acids research · 2026Article
- Chemical engineering of CRISPR-Cas systems for therapeutic application.Nature reviews. Drug discovery · 2025Review
- NMR structures and magnetic force spectroscopy studies of small molecules binding to models of an RNA CAG repeat expansion.bioRxiv : the preprint server for biology · 2024Article
- Constraints on the emergence of RNA through non-templated primer extension with mixtures of potentially prebiotic nucleotides.Nucleic acids research · 2024Article
- High-Fidelity RNA Copying via 2',3'-Cyclic Phosphate Ligation.Journal of the American Chemical Society · 2024Article
- Minimal RNA self-reproduction discovered from a random pool of oligomers.Chemical science · 2023Article
- Design, Synthesis, and Characterization of a Novel 2'-5'-Linked Amikacin-Binding Aptamer: An Experimental and MD Simulation Study.ACS chemical biology · 2022Article
- Peptides before and during the nucleotide world: an origins story emphasizing cooperation between proteins and nucleic acids.Journal of the Royal Society, Interface · 2022Review
- Site-specific Incorporation of 2',5'-Linked Nucleic Acids Enhances Therapeutic Profile of Antisense Oligonucleotides.ACS medicinal chemistry letters · 2021Article
- Hybrid DNA/RNA nanostructures with 2'-5' linkages.Nanoscale · 2020Article
- Base pairing, structural and functional insights into N4-methylcytidine (m4C) and N4,N4-dimethylcytidine (m42C) modified RNA.Nucleic acids research · 2020Article
- In vitro Selection of Chemically Modified DNAzymes.ChemistryOpen · 2020Review
- Deep sequencing of non-enzymatic RNA primer extension.Nucleic acids research · 2020Article
- Effect of 2'-5'/3'-5' phosphodiester linkage heterogeneity on RNA interference.Nucleic acids research · 2020Article
- The role of sugar-backbone heterogeneity and chimeras in the simultaneous emergence of RNA and DNA.Nature chemistry · 2019Article
- Review of Emerging Japanese Encephalitis Virus: New Aspects and Concepts about Entry into the Brain and Inter-Cellular Spreading.Pathogens (Basel, Switzerland) · 2019Review
- Extensive CRISPR RNA modification reveals chemical compatibility and structure-activity relationships for Cas9 biochemical activity.Nucleic acids research · 2019Article
- Circular RNAs as Therapeutic Agents and Targets.Frontiers in physiology · 2018Review
- Insight into the mechanism of nonenzymatic RNA primer extension from the structure of an RNA-GpppG complex.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Structural insights into RNA duplexes with multiple 2΄-5΄-linkages.Nucleic acids research · 2017Article
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6 authors.
Funding
Abstract
The mixture of 2'-5' and 3'-5' linkages generated during the nonenzymatic replication of RNA has long been regarded as a central problem for the origin of the RNA world. However, we recently observed that both a ribozyme and an RNA aptamer retain considerable functionality in the presence of prebiotically plausible levels of linkage heterogeneity. To better understand the RNA structure and function in the presence of backbone linkage heterogeneity, we obtained high-resolution X-ray crystal structures of a native 10-mer RNA duplex (1.32 Å) and two variants: one containing one 2'-5' linkage per strand (1.55 Å) and one containing three such linkages per strand (1.20 Å). We found that RNA duplexes adjust their local structures to accommodate the perturbation caused by 2'-5' linkages, with the flanking nucleotides buffering the disruptive effects of the isomeric linkage and resulting in a minimally altered global structure. Although most 2'-linked sugars were in the expected 2'-endo conformation, some were partially or fully in the 3'-endo conformation, suggesting that the energy difference between these conformations was relatively small. Our structural and molecular dynamic studies also provide insight into the diminished thermal and chemical stability of the duplex state associated with the presence of 2'-5' linkages. Our results contribute to the view that a low level of 2'-5' substitution would not have been fatal in an early RNA world and may in contrast have been helpful for both the emergence of nonenzymatic RNA replication and the early evolution of functional RNAs.
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