Nucleic acids

  • Article
    | Open Access

    Ligand-oligonucleotide interactions can integrate both small molecules and proteins into nucleic acid-based circuits. Here the authors design ligand-aptamer complexes to control strand-displacement reactions for versatile ligand transduction.

    • Qiu-Long Zhang
    • , Liang-Liang Wang
    •  & Liang Xu
  • Article
    | Open Access

    PMOs (phosphorodiamidate morpholino oligomers) have huge potential for antisense therapy but complex and slow synthesis limits application. Here, the authors report the development of automated flow synthesis methods which reduce nucleobase coupling times from hours to minutes removing human errors and allow for high-throughput production.

    • Chengxi Li
    • , Alex J. Callahan
    •  & Bradley L. Pentelute
  • Article
    | Open Access

    A world preceding the prebiotic RNA-world may have been based on xeno nucleic acids (XNAs), but their replication likely did not require enzymes. Here, the authors demonstrate template-directed non-enzymatic synthesis of an XNA, acyclic l-threoninol nucleic acid, via chemical ligation mediated by N-cyanoimidazole, and achieve a pseudo-primer extension of this XNA with all four nucleobases.

    • Keiji Murayama
    • , Hikari Okita
    •  & Hiroyuki Asanuma
  • Article
    | Open Access

    Short hairpin RNAs can be used to modulate and regulate gene expression. Here the authors generate chimeric RNAs that interact with the photoreceptor PAL, allowing for optoribogenetic control of cell physiology.

    • Sebastian Pilsl
    • , Charles Morgan
    •  & Günter Mayer
  • Article
    | Open Access

    Riboswitches are conserved RNA domains located in the non-coding region of mRNA that recognize cellular metabolites and, in turn, regulate gene expression. Here the authors report the structure of the recently identified SAM-VI riboswitch and provide insight into its mechanism of ligand discrimination.

    • Aiai Sun
    • , Catherina Gasser
    •  & Aiming Ren
  • Article
    | Open Access

    Transfer RNA (tRNA) is regulated by RNA modifications. Here the authors employ time-resolved NMR to monitor modifications of yeast tRNAPhe in cellular extracts, revealing a sequential order and cross-talk between modifications.

    • Pierre Barraud
    • , Alexandre Gato
    •  & Carine Tisné
  • Article
    | Open Access

    For CRISPR-Cas9 genome editing, Cas9 protein is guided to its target by single guide (sg) RNA. Here, the authors synthesised sgRNAs via convergent ‘click’ ligation of variable 20-mer RNAs that target the genome and a Cas9-binding 79-mer chimeric RNA/2´-OMe RNA of fixed sequence in a single tube.

    • Lapatrada Taemaitree
    • , Arun Shivalingam
    •  & Tom Brown
  • Article
    | Open Access

    Amphihelical antimicrobial peptides (AMPs) are bactericidal host defense factors, but their function as immunomodulators is emerging. Here the authors show that several AMPs organize DNA into periodic nanocrystals by self-assembling into superhelical protofibril scaffolds, which potentiates DNA sensing by TLR9.

    • Ernest Y. Lee
    • , Changsheng Zhang
    •  & Gerard C. L. Wong
  • Article
    | Open Access

    Membraneless compartments have been theorized to be prebiotic micro-compartments as they spontaneously encapsulate RNA and proteins. Here, the authors report membraneless compartments can enhance RNA chemistries, affecting template directed RNA polymerization and stimulating nucleic acid enzymes.

    • Raghav R. Poudyal
    • , Rebecca M. Guth-Metzler
    •  & Philip C. Bevilacqua
  • Article
    | Open Access

    The recognition of the mRNA codon by the tRNA anticodon is crucial for protein synthesis. Here the authors introduce non-standard nucleotides in bacterial and eukaryotic mRNA to reveal the minimal hydrogen bond requirement of codon-anticodon interaction for efficient and accurate translation.

    • Thomas Philipp Hoernes
    • , Klaus Faserl
    •  & Matthias David Erlacher
  • Article
    | Open Access

    Targeting noncoding nucleic acids with small molecules represents an important and significant challenge in chemical biology and drug discovery. Here the authors characterize DC-34, a small molecule that exhibits selective binding to specific G4 structures, and provide a structural basis for its selectivity

    • David R. Calabrese
    • , Xiang Chen
    •  & John S. Schneekloth Jr.
  • Article
    | Open Access

    The laboratory-evolved polymerase Kod-RI catalyzes α-L-threose nucleic acid (TNA) synthesis. Here, the authors present Kod-RI crystal structures that give insights into how TNA triphosphates are selected and extended in a template-dependent manner, which will help to engineer improved TNA polymerases for synthetic genetics applications.

    • Nicholas Chim
    • , Changhua Shi
    •  & John C. Chaput
  • Article
    | Open Access

    Identification of inhibitors can be accelerated by using the target as a template for ligand formation. Here the authors show that DNA-functionalised magnetic nanoparticles guide templating of G-quadruplex bindingc-MYCinhibitors from an array of building blocks, and can be isolated by magnetic decanting.

    • Deepanjan Panda
    • , Puja Saha
    •  & Jyotirmayee Dash
  • Article
    | Open Access

    Expansion of the trinucleotide GAA within an intronic FXN RNA can cause Friedreich's Ataxia (FRDA), an incurable genetic disorder. Here, the authors show that anti-GAA duplex RNAs or single-stranded locked nucleic acids increases FXN protein expression in patient-derived cells to levels similar to wild-type cells.

    • Liande Li
    • , Masayuki Matsui
    •  & David R. Corey
  • Article
    | Open Access

    Point-of-care analytical devices are of interest for diagnostic applications where larger scale laboratory instruments are not feasible or available. Here, the authors present a direct read-out colorimetric sensor which uses catalytic gas production to visualize picomolar concentrations of DNA.

    • Justin D. Besant
    • , Jagotamoy Das
    •  & Shana O. Kelley