Nucleic acids articles within Nature Communications

Featured

• Article
  09 April 2024 | Open Access

  Expedient production of site specifically nucleobase-labelled or hypermodified RNA with engineered thermophilic DNA polymerases

  A general method for enzymatic synthesis of base-modified RNA was developed using engineered thermostable DNA polymerases enabling introduction of site-specific modifications or synthesis of hypermodified RNA not accessible by in vitro transcription.

  • Mária Brunderová
  • , Vojtěch Havlíček
  •  & Michal Hocek

• Article
  21 March 2024 | Open Access

  Late-stage guanine C8–H alkylation of nucleosides, nucleotides, and oligonucleotides via photo-mediated Minisci reaction

  Chemically modified nucleobases and oligonucleotides are essential in several fields but introducing functional groups into nucleobases requires laborious chemical synthesis. Here, the authors report site-selective alkylation at the C8-position of guanines in guanosine, GMP, GDP, and GTP, as well as late-stage alkylation of RNA/DNA oligonucleotides through photomediated Minisci reaction.

  • Ruoqian Xie
  • , Wanlu Li
  •  & Gang Chen

• Article
  15 February 2024 | Open Access

  Trabectedin derails transcription-coupled nucleotide excision repair to induce DNA breaks in highly transcribed genes

  The antitumor drug trabectedin is more toxic to DNA-repair-proficient cells. Here the authors show that this is caused by persistent DNA breaks induced from an abortive repair reaction and develop “TRABI-Seq” to map the breaks to transcribed regions of the genome. Trabectedin may thus be used as a diagnostic and therapeutic in precision oncology.

  • Kook Son
  • , Vakil Takhaveev
  •  & Orlando D. Schärer

• Article
  12 February 2024 | Open Access

  Liquid crystalline inverted lipid phases encapsulating siRNA enhance lipid nanoparticle mediated transfection

  The authors display the bottom-up design, assembly, and in-depth characterization of defined lipid-RNA structures in the core of lipid nanoparticles. The inverted structures are thermostable and provide better transfection over lamellar structures.

  • Roy Pattipeiluhu
  • , Ye Zeng
  •  & Thomas H. Sharp

• Article
  15 November 2023 | Open Access

  Profiling stress-triggered RNA condensation with photocatalytic proximity labeling

  Stress granules (SGs) are highly dynamic cytoplasmic membraneless organelles that assemble when cells are challenged by stress. Herein, the authors apply a proximity-dependent RNA labeling method, CAP-seq, to comprehensively investigate the content of SG-proximal transcriptome and the dynamic change in SG-proximal transcriptome along the time course of granule assembly and disassembly processes in live mammalian cells.

  • Ziqi Ren
  • , Wei Tang
  •  & Peng Zou

• Article
  26 October 2023 | Open Access

  Enzymatic synthesis and nanopore sequencing of 12-letter supernumerary DNA

  Unnatural base pairing xenonucleic acids (XNAs) can be used to expand life’s alphabet beyond ATGC. Here, authors show strategies for enzymatic synthesis and next-generation nanopore sequencing of XNA base pairs for reading and writing 12-letter DNA (ATGCBSPZXKJV).

  • Hinako Kawabe
  • , Christopher A. Thomas
  •  & Jorge A. Marchand

• Article
  17 August 2023 | Open Access

  Extensive breaking of genetic code degeneracy with non-canonical amino acids

  Genetic code expansion is limited by the degeneracy of the 61 sense codons which encode for only 20 amino acids. Here, the authors show that by combining hyperaccurate ribosomes and in vitro transcribed tRNAs, dramatic and extensive breaking of sense codon degeneracy can be achieved.

  • Clinton A. L. McFeely
  • , Bipasana Shakya
  •  & Matthew C. T. Hartman

• Article
  13 July 2023 | Open Access

  Hidden modes of DNA binding by human nuclear receptors

  Nuclear receptors (NR) are drug-responsive master regulators. Here, authors map DNA binding profiles of all human NRs. Their MinSeq Find algorithm identifies masked NR binding sites in genomes and maps ~10% of orphan SNPs linked to numerous diseases.

  • Devesh Bhimsaria
  • , José A. Rodríguez-Martínez
  •  & Aseem Z. Ansari

• Article
  27 April 2023 | Open Access

  Chemical evolution of an autonomous DNAzyme with allele-specific gene silencing activity

  Low activity currently prevents the wider use of DNA enzymes (DNAzymes). Here the authors report the chemical evolution of a DNAzyme with high catalytic activity under near physiological conditions: the enzyme achieves ~65 turnovers in 30 minutes.

  • Kim Nguyen
  • , Turnee N. Malik
  •  & John C. Chaput

• Article
  13 January 2023 | Open Access

  Structural basis of transcription recognition of a hydrophobic unnatural base pair by T7 RNA polymerase

  T7 RNA polymerase (RNAP) is widely used for synthesizing RNA molecules with synthetic modifications and unnatural base pairs (UBPs). Here, authors show the structural basis of how UBPs are recognized as template and substrate, providing mechanistic insights into UBP transcription by T7 RNAP.

  • Juntaek Oh
  • , Michiko Kimoto
  •  & Dong Wang

• Article
  10 January 2023 | Open Access

  Additive-controlled asymmetric iodocyclization enables enantioselective access to both α- and β-nucleosides

  Nucleosides and their analogs are pharmacologically important molecules. Here, the authors report an additive-controlled stereodivergent iodocyclization method for the selective synthesis of α- or β-nucleosides.

  • Qi Wang
  • , Jiayi Mu
  •  & Fener Chen

• Article
  29 November 2022 | Open Access

  Shedding light on the base-pair opening dynamics of nucleic acids in living human cells

  Base-pair opening is important for nucleic acids to exert biological functions, but studying its dynamics inside living cells is challenging. Here, the authors determine the base-pair opening kinetics of hairpin and G-quadruplex structures inside living human cells by the in-cell NMR technique, and demonstrate a difference in dynamics of nucleic acids between in-cell and in vitro conditions.

  • Yudai Yamaoki
  • , Takashi Nagata
  •  & Masato Katahira

• Article
  16 November 2022 | Open Access

  XNAzymes targeting the SARS-CoV-2 genome inhibit viral infection

  RNA viruses have been responsible for large-scale epidemics and pandemics throughout the last few centuries. Here, the authors show the design, synthesis and screening of artificial RNA endonuclease XNAzymes capable of cleaving genomic SARS-CoV-2 RNA and self-assembling into enzymatic nanostructures inhibiting cellular viral replication.

  • Pehuén Pereyra Gerber
  • , Maria J. Donde
  •  & Alexander I. Taylor

• Article
  02 November 2022 | Open Access

  HIF1α-AS1 is a DNA:DNA:RNA triplex-forming lncRNA interacting with the HUSH complex

  Using a composite bioinformatics approach, the DNA:DNA:RNA triplex-forming lncRNAs HIF1α-AS1 was identified in human endothelial cells which recruits an epigenetic silencing complex to limit expression of triplex target genes.

  • Matthias S. Leisegang
  • , Jasleen Kaur Bains
  •  & Ralf P. Brandes

• Article
  29 October 2022 | Open Access

  Microfluidic space coding for multiplexed nucleic acid detection via CRISPR-Cas12a and recombinase polymerase amplification

  Fast, low-cost and multiplexed nucleic acid detection is challenging. Here the authors report a strategy that couples microfluidic space coding, CRISPRCas12a, and multiplex RPA for the rapid detection of up to 30 targets with only one fluorescent probe.

  • Zhichen Xu
  • , Dongjuan Chen
  •  & Maili Liu

• Article
  08 October 2022 | Open Access

  Controllable DNA hybridization by host–guest complexation-mediated ligand invasion

  Direct dissociation of nucleic acid duplex structures without heating or specific binding proteins is challenging. Here the authors use the cucurbit[7]uril-based host–guest system to construct a ligand-invasion pathway for controllable DNA hybridisation.

  • Lin Xiao
  • , Liang-Liang Wang
  •  & Liang Xu

• Article
  26 August 2022 | Open Access

  Efficient DNA fluorescence labeling via base excision trapping

  Methods for fluorescently labelling DNAs are expensive and labour-intensive. Here the authors report an in situ DNA labelling strategy for oligonucleotides as well as dsDNA that makes use of aldehyde-reactive rotor dyes to trap AP sites resulting from excision of deaminated DNA bases.

  • Yong Woong Jun
  • , Emily M. Harcourt
  •  & Eric T. Kool

• Article
  30 June 2022 | Open Access

  Simple synthesis of massively parallel RNA microarrays via enzymatic conversion from DNA microarrays

  RNA microarrays have many potential applications, but are difficult to produce. Here, the AUs present a method for converting commercial, customizable DNA microarrays into RNA microarrays using an accessible three-step process involving primer photocrosslinking, extension, and template degradation.

  • Erika Schaudy
  • , Kathrin Hölz
  •  & Mark M. Somoza

• Article
  09 May 2022 | Open Access

  Targeting double-strand break indel byproducts with secondary guide RNAs improves Cas9 HDR-mediated genome editing efficiencies

  Programmable double-strand DNA breaks (DSBs) can be harnessed for precision genome editing through manipulation of the homology-directed repair (HDR) pathway. Here the authors report the development of the double tap - double tap implements secondary gRNAs which target Cas9 to common indel sequences and provides a second chance at HDR.

  • Zsolt Bodai
  • , Alena L. Bishop
  •  & Alexis C. Komor

• Article
  28 March 2022 | Open Access

  Structural basis of R-loop recognition by the S9.6 monoclonal antibody

  The S9.6 monoclonal antibody is widely used to map R-loops genome wide. Here, Bou-Nader et al., define the nucleic acid-binding specificity of S9.6 and report its crystal structures free and bound to a hybrid, which reveal the asymmetric recognition of the RNA and DNA strands and its A-form conformation.

  • Charles Bou-Nader
  • , Ankur Bothra
  •  & Jinwei Zhang

• Article
  15 November 2021 | Open Access

  Gene editing with CRISPR-Cas12a guides possessing ribose-modified pseudoknot handles

  Development of Cas12a for human therapeutics and diagnostics may significantly benefit from, or even require, chemical modification of its guide RNA. Here the authors show that the noncanonical 5′ pseudoknot structure of the AsCas12a crRNA guide can be heavily modified and still retain very high editing activity in cells and trans cleavage activity in vitro.

  • Eman A. Ageely
  • , Ramadevi Chilamkurthy
  •  & Keith T. Gagnon

• Article
  06 October 2021 | Open Access

  A chemical probe based on the PreQ₁ metabolite enables transcriptome-wide mapping of binding sites

  The small modified nucleotide PreQ1 binds to the PreQ1 riboswitch and regulates gene expression by inducing RNA conformation change. Here the authors design and characterize a specific preQ1-derived probe by x-ray crystallography, mass spectral analysis and transcriptome-wide using Chem-CLIP.

  • Sumirtha Balaratnam
  • , Curran Rhodes
  •  & John S. Schneekloth Jr

• Article
  24 August 2021 | Open Access

  A non-enzymatic, isothermal strand displacement and amplification assay for rapid detection of SARS-CoV-2 RNA

  The reliance on enzymes in SARS-CoV-2 RNA detection imposes limits on transport and storage conditions. Here the authors use non-enzymatic isothermal amplification to detect RNA with no need for reverse transcription.

  • Mohsen Mohammadniaei
  • , Ming Zhang
  •  & Yi Sun

• Article
  02 August 2021 | Open Access

  A kinetically controlled platform for ligand-oligonucleotide transduction

  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
  20 July 2021 | Open Access

  Fully automated fast-flow synthesis of antisense phosphorodiamidate morpholino oligomers

  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
  05 February 2021 | Open Access

  Nonenzymatic polymerase-like template-directed synthesis of acyclic l-threoninol nucleic acid

  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
  24 September 2020 | Open Access

  Optoribogenetic control of regulatory RNA molecules

  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
  03 January 2020 | Open Access

  Conditional control of RNA-guided nucleic acid cleavage and gene editing

  Constituitively active CRISPR systems have the risk of adverse off-target effects. Here the authors use chemical masking and activation of gRNA to control activity.

  • Shao-Ru Wang
  • , Ling-Yu Wu
  •  & Xiang Zhou

• Article
  16 December 2019 | Open Access

  SAM-VI riboswitch structure and signature for ligand discrimination

  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
  29 July 2019 | Open Access

  Time-resolved NMR monitoring of tRNA maturation

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

  • Pierre Barraud
  • , Alexandre Gato
  •  & Carine Tisné

• Article
  08 April 2019 | Open Access

  An artificial triazole backbone linkage provides a split-and-click strategy to bioactive chemically modified CRISPR sgRNA

  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
  04 March 2019 | Open Access

  Helical antimicrobial peptides assemble into protofibril scaffolds that present ordered dsDNA to TLR9

  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
  30 January 2019 | Open Access

  Template-directed RNA polymerization and enhanced ribozyme catalysis inside membraneless compartments formed by coacervates

  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

• Comment
  12 December 2018 | Open Access

  Non-canonical nucleosides and chemistry of the emergence of life

  • Sidney Becker
  • , Christina Schneider
  •  & Thomas Carell

• Comment
  12 December 2018 | Open Access

  Prebiotic plausibility and networks of paradox-resolving independent models

  • Steven A. Benner

• Comment
  12 December 2018 | Open Access

  Life as a guide to prebiotic nucleotide synthesis

  • Stuart A. Harrison
  •  & Nick Lane

• Comment
  12 December 2018 | Open Access

  Prebiotic chemistry and human intervention

  • Clemens Richert

• Comment
  12 December 2018 | Open Access

  Searching for lost nucleotides of the pre-RNA World with a self-refining model of early Earth

  • Nicholas V. Hud

• Comment
  12 December 2018 | Open Access

  Prebiotic nucleic acids need space to grow

  • Daniel Whitaker
  •  & Matthew W. Powner

• Comment
  12 December 2018 | Open Access

  Experimentally investigating the origin of DNA/RNA on early Earth

  • Ramanarayanan Krishnamurthy

• Article
  19 November 2018 | Open Access

  Translation of non-standard codon nucleotides reveals minimal requirements for codon-anticodon interactions

  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
  12 October 2018 | Open Access

  Chemical and structural studies provide a mechanistic basis for recognition of the MYC G-quadruplex

  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
  11 June 2018 | Open Access

  An anionic phthalocyanine decreases NRAS expression by breaking down its RNA G-quadruplex

  Hyperactivity of the gene NRAS contributes to the proliferation and metastatic nature of many types of cancer cells. Here, the authors show that NRAS can be controlled by an anionic phthalocyanine coordinating Zn²⁺ in combination with photo-irradiation.

  • Keiko Kawauchi
  • , Wataru Sugimoto
  •  & Daisuke Miyoshi

• Article
  11 June 2018 | Open Access

  Modular cell-internalizing aptamer nanostructure enables targeted delivery of large functional RNAs in cancer cell lines

  Large RNAs and ribonucleoprotein complexes have shown potential as novel therapeutic agents, but their targeted delivery to cells is still challenging. Here the authors present a modular aptamer nanostructure for intracellular delivery of RNAs up to 250 nucleotides to cancer cells.

  • David Porciani
  • , Leah N. Cardwell
  •  & Donald H. Burke

• Article
  24 January 2018 | Open Access

  Comprehensive profiling of the ligand binding landscapes of duplexed aptamer families reveals widespread induced fit

  Duplexed aptamers are a common biosensor format; however, how complementary strand sequence, length, and position modulate ligand binding is not well understood. Here, the authors introduce ACE-Scan to comprehensively map binding landscapes, uncovering hotspots of enhanced binding by induced fit.

  • Jeffrey D. Munzar
  • , Andy Ng
  •  & David Juncker

• Article
  27 November 2017 | Open Access

  Structural basis for TNA synthesis by an engineered TNA polymerase

  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
  14 July 2017 | Open Access

  Target guided synthesis using DNA nano-templates for selectively assembling a G-quadruplex binding c-MYC inhibitor

  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
  04 February 2016 | Open Access

  Activating frataxin expression by repeat-targeted nucleic acids

  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
  22 April 2015 | Open Access

  Ultrasensitive visual read-out of nucleic acids using electrocatalytic fluid displacement

  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

• Article
  23 August 2011 | Open Access

  Freely orbiting magnetic tweezers to directly monitor changes in the twist of nucleic acids

  Rotational motion and torsional strain affects DNA replication, transcription and repair. Lipfertet al. have developed a new technique that uses freely orbiting magnetic tweezers to measure equilibrium fluctuations and determine the twist of tethered nucleic acid molecules.

  • Jan Lipfert
  • , Matthew Wiggin
  •  & Nynke H. Dekker