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  • 3-Dimensional architecture of the human multi-tRNA synthetase complex
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-07-09
    Krishnendu Khan; Camelia Baleanu-Gogonea; Belinda Willard; Valentin Gogonea; Paul L Fox

    In mammalian cells, eight cytoplasmic aminoacyl-tRNA synthetases (AARS), and three non-synthetase proteins, reside in a large multi-tRNA synthetase complex (MSC). AARSs have critical roles in interpretation of the genetic code during protein synthesis, and in non-canonical functions unrelated to translation. Nonetheless, the structure and function of the MSC remain unclear. Partial or complete crystal

    更新日期:2020-07-09
  • Resolving Toxic DNA repair intermediates in every E. coli replication cycle: critical roles for RecG, Uup and RadD
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-07-09
    Zachary J Romero; Stefanie H Chen; Thomas Armstrong; Elizabeth A Wood; Antoine Oijen van; Andrew Robinson; Michael M Cox

    DNA lesions or other barriers frequently compromise replisome progress. The SF2 helicase RecG is a key enzyme in the processing of postreplication gaps or regressed forks in Escherichia coli. A deletion of the recG gene renders cells highly sensitive to a range of DNA damaging agents. Here, we demonstrate that RecG function is at least partially complemented by another SF2 helicase, RadD. A ΔrecGΔradD

    更新日期:2020-07-09
  • Switching the activity of Taq polymerase using clamp-like triplex aptamer structure
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-07-09
    Yingxin Hu; Zhiyu Wang; Zhekun Chen; Linqiang Pan

    In nature, allostery is the principal approach for regulating cellular processes and pathways. Inspired by nature, structure-switching aptamer-based nanodevices are widely used in artificial biotechnologies. However, the canonical aptamer structures in the nanodevices usually adopt a duplex form, which limits the flexibility and controllability. Here, a new regulating strategy based on a clamp-like

    更新日期:2020-07-09
  • A critical analysis of methods used to investigate the cellular uptake and subcellular localization of RNA therapeutics
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-07-09
    Kirsten Deprey; Nefeli Batistatou; Joshua A Kritzer

    RNA therapeutics are a promising strategy to treat genetic diseases caused by the overexpression or aberrant splicing of a specific protein. The field has seen major strides in the clinical efficacy of this class of molecules, largely due to chemical modifications and delivery strategies that improve nuclease resistance and enhance cell penetration. However, a major obstacle in the development of RNA

    更新日期:2020-07-09
  • NC2 complex is a key factor for the activation of catalase-3 transcription by regulating H2A.Z deposition
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-07-07
    Guofei Cui; Qing Dong; Jiabin Duan; Chengcheng Zhang; Xiao Liu; Qun He

    Negative cofactor 2 (NC2), including two subunits NC2α and NC2β, is a conserved positive/negative regulator of class II gene transcription in eukaryotes. It is known that NC2 functions by regulating the assembly of the transcription preinitiation complex. However, the exact role of NC2 in transcriptional regulation is still unclear. Here, we reveal that, in Neurospora crassa, NC2 activates catalase-3

    更新日期:2020-07-09
  • Bypass of DNA interstrand crosslinks by a Rev1–DNA polymerase ζ complex
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-07-07
    Rachel Bezalel-Buch; Young K Cheun; Upasana Roy; Orlando D Schärer; Peter M Burgers

    DNA polymerase ζ (Pol ζ) and Rev1 are essential for the repair of DNA interstrand crosslink (ICL) damage. We have used yeast DNA polymerases η, ζ and Rev1 to study translesion synthesis (TLS) past a nitrogen mustard-based interstrand crosslink (ICL) with an 8-atom linker between the crosslinked bases. The Rev1–Pol ζ complex was most efficient in complete bypass synthesis, by 2–3 fold, compared to Pol

    更新日期:2020-07-09
  • Structures of mammalian GLD-2 proteins reveal molecular basis of their functional diversity in mRNA and microRNA processing
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-07-07
    Xiao-Yan Ma; Hong Zhang; Jian-Xiong Feng; Jia-Li Hu; Bing Yu; Li Luo; Yu-Lu Cao; Shuang Liao; Jichang Wang; Song Gao

    The stability and processing of cellular RNA transcripts are efficiently controlled via non-templated addition of single or multiple nucleotides, which is catalyzed by various nucleotidyltransferases including poly(A) polymerases (PAPs). Germline development defective 2 (GLD-2) is among the first reported cytoplasmic non-canonical PAPs that promotes the translation of germline-specific mRNAs by extending

    更新日期:2020-07-09
  • Variance-adjusted Mahalanobis (VAM): a fast and accurate method for cell-specific gene set scoring
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-07-07
    Hildreth Robert Frost

    Statistical analysis of single cell RNA-sequencing (scRNA-seq) data is hindered by high levels of technical noise and inflated zero counts. One promising approach for addressing these challenges is gene set testing, or pathway analysis, which can mitigate sparsity and noise, and improve interpretation and power, by aggregating expression data to the pathway level. Unfortunately, methods optimized for

    更新日期:2020-07-09
  • Taxonomic classification method for metagenomics based on core protein families with Core-Kaiju
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-07-07
    Anna Tovo; Peter Menzel; Anders Krogh; Marco Cosentino Lagomarsino; Samir Suweis

    Characterizing species diversity and composition of bacteria hosted by biota is revolutionizing our understanding of the role of symbiotic interactions in ecosystems. Determining microbiomes diversity implies the assignment of individual reads to taxa by comparison to reference databases. Although computational methods aimed at identifying the microbe(s) taxa are available, it is well known that inferences

    更新日期:2020-07-09
  • Comprehensive nucleosome interactome screen establishes fundamental principles of nucleosome binding
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-07-07
    Aleksandra Skrajna; Dennis Goldfarb; Katarzyna M Kedziora; Emily M Cousins; Gavin D Grant; Cathy J Spangler; Emily H Barbour; Xiaokang Yan; Nathaniel A Hathaway; Nicholas G Brown; Jeanette G Cook; Michael B Major; Robert K McGinty

    Nuclear proteins bind chromatin to execute and regulate genome-templated processes. While studies of individual nucleosome interactions have suggested that an acidic patch on the nucleosome disk may be a common site for recruitment to chromatin, the pervasiveness of acidic patch binding and whether other nucleosome binding hot-spots exist remain unclear. Here, we use nucleosome affinity proteomics

    更新日期:2020-07-07
  • DNA backbone interactions impact the sequence specificity of DNA sulfur-binding domains: revelations from structural analyses
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-07-04
    Hao Yu; Jiayi Li; Guang Liu; Gong Zhao; Yuli Wang; Wenyue Hu; Zixin Deng; Geng Wu; Jianhua Gan; Yi-Lei Zhao; Xinyi He

    The sulfur atom of phosphorothioated DNA (PT-DNA) is coordinated by a surface cavity in the conserved sulfur-binding domain (SBD) of type IV restriction enzymes. However, some SBDs cannot recognize the sulfur atom in some sequence contexts. To illustrate the structural determinants for sequence specificity, we resolved the structure of SBDSpr, from endonuclease SprMcrA, in complex with DNA of GPSGCC

    更新日期:2020-07-05
  • RADX condenses single-stranded DNA to antagonize RAD51 loading
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-07-04
    Hongshan Zhang; Jeffrey M Schaub; Ilya J Finkelstein

    RADX is a mammalian single-stranded DNA-binding protein that stabilizes telomeres and stalled replication forks. Cellular biology studies have shown that the balance between RADX and Replication Protein A (RPA) is critical for DNA replication integrity. RADX is also a negative regulator of RAD51-mediated homologous recombination at stalled forks. However, the mechanism of RADX acting on DNA and its

    更新日期:2020-07-05
  • CASC3 promotes transcriptome-wide activation of nonsense-mediated decay by the exon junction complex
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-07-04
    Jennifer V Gerbracht; Volker Boehm; Thiago Britto-Borges; Sebastian Kallabis; Janica L Wiederstein; Simona Ciriello; Dominik U Aschemeier; Marcus Krüger; Christian K Frese; Janine Altmüller; Christoph Dieterich; Niels H Gehring

    The exon junction complex (EJC) is an essential constituent and regulator of spliced messenger ribonucleoprotein particles (mRNPs) in metazoans. As a core component of the EJC, CASC3 was described to be pivotal for EJC-dependent nuclear and cytoplasmic processes. However, recent evidence suggests that CASC3 functions differently from other EJC core proteins. Here, we have established human CASC3 knockout

    更新日期:2020-07-05
  • Bulk and single-molecule analysis of a bacterial DNA2-like helicase–nuclease reveals a single-stranded DNA looping motor
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-07-04
    Oliver J Wilkinson; Carolina Carrasco; Clara Aicart-Ramos; Fernando Moreno-Herrero; Mark S Dillingham

    DNA2 is an essential enzyme involved in DNA replication and repair in eukaryotes. In a search for homologues of this protein, we identified and characterised Geobacillus stearothermophilus Bad, a bacterial DNA helicase–nuclease with similarity to human DNA2. We show that Bad contains an Fe-S cluster and identify four cysteine residues that are likely to co-ordinate the cluster by analogy to DNA2. The

    更新日期:2020-07-05
  • IMPLICON: an ultra-deep sequencing method to uncover DNA methylation at imprinted regions
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-07-04
    Tajda Klobučar; Elisa Kreibich; Felix Krueger; Maria Arez; Duarte Pólvora-Brandão; Ferdinand von Meyenn; Simão Teixeira da Rocha; Melanie Eckersley-Maslin

    Genomic imprinting is an epigenetic phenomenon leading to parental allele-specific expression. Dosage of imprinted genes is crucial for normal development and its dysregulation accounts for several human disorders. This unusual expression pattern is mostly dictated by differences in DNA methylation between parental alleles at specific regulatory elements known as imprinting control regions (ICRs).

    更新日期:2020-07-05
  • Transcription of intragenic CpG islands influences spatiotemporal host gene pre-mRNA processing
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-07-04
    Samuele M Amante; Bertille Montibus; Michael Cowley; Nikolaos Barkas; Jessica Setiadi; Heba Saadeh; Joanna Giemza; Stephania Contreras-Castillo; Karin Fleischanderl; Reiner Schulz; Rebecca J Oakey

    Alternative splicing (AS) and alternative polyadenylation (APA) generate diverse transcripts in mammalian genomes during development and differentiation. Epigenetic marks such as trimethylation of histone H3 lysine 36 (H3K36me3) and DNA methylation play a role in generating transcriptome diversity. Intragenic CpG islands (iCGIs) and their corresponding host genes exhibit dynamic epigenetic and gene

    更新日期:2020-07-05
  • Highly efficient ‘hit-and-run’ genome editing with unconcentrated lentivectors carrying Vpr.Prot.Cas9 protein produced from RRE-containing transcripts
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-07-03
    Ivana Indikova; Stanislav Indik

    The application of gene-editing technology is currently limited by the lack of safe and efficient methods to deliver RNA-guided endonucleases to target cells. We engineered lentivirus-based nanoparticles to co-package the U6-sgRNA template and the CRISPR-associated protein 9 (Cas9) fused with a virion-targeted protein Vpr (Vpr.Prot.Cas9), for simultaneous delivery to cells. Equal spatiotemporal control

    更新日期:2020-07-05
  • A point mutation in the nuclease domain of MLH3 eliminates repeat expansions in a mouse stem cell model of the Fragile X-related disorders
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-07-03
    Bruce E Hayward; Peter J Steinbach; Karen Usdin

    The Fragile X-related disorders (FXDs) are Repeat Expansion Diseases, genetic disorders that result from the expansion of a disease-specific microsatellite. In those Repeat Expansion Disease models where it has been examined, expansion is dependent on functional mismatch repair (MMR) factors, including MutLγ, a heterodimer of MLH1/MLH3, one of the three MutL complexes found in mammals and a minor player

    更新日期:2020-07-05
  • Rph1 coordinates transcription of ribosomal protein genes and ribosomal RNAs to control cell growth under nutrient stress conditions
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-07-03
    Wen-Jie Shu; Runfa Chen; Zhao-Hong Yin; Feng Li; Heng Zhang; Hai-Ning Du

    Coordinated regulation of ribosomal RNA (rRNA) synthesis and ribosomal protein gene (RPG) transcription by eukaryotic RNA polymerases (RNAP) is a key requirement for growth control. Although evidence for balance between RNPI-dependent 35S rRNA production and RNAPII-mediated RPG transcription have been described, the molecular basis is still obscure. Here, we found that Rph1 modulates the transcription

    更新日期:2020-07-05
  • Embryonic tissue differentiation is characterized by transitions in cell cycle dynamic-associated core promoter regulation
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-07-03
    Joseph W Wragg; Leonie Roos; Dunja Vucenovic; Nevena Cvetesic; Boris Lenhard; Ferenc Müller

    The core-promoter, a stretch of DNA surrounding the transcription start site (TSS), is a major integration-point for regulatory-signals controlling gene-transcription. Cellular differentiation is marked by divergence in transcriptional repertoire and cell-cycling behaviour between cells of different fates. The role promoter-associated gene-regulatory-networks play in development-associated transitions

    更新日期:2020-07-05
  • Anti-inflammatory functions of the glucocorticoid receptor require DNA binding
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-07-03
    Laura Escoter-Torres; Franziska Greulich; Fabiana Quagliarini; Michael Wierer; Nina Henriette Uhlenhaut

    The glucocorticoid receptor is an important immunosuppressive drug target and metabolic regulator that acts as a ligand-gated transcription factor. Generally, GR’s anti-inflammatory effects are attributed to the silencing of inflammatory genes, while its adverse effects are ascribed to the upregulation of metabolic targets. GR binding directly to DNA is proposed to activate, whereas GR tethering to

    更新日期:2020-07-05
  • STing: accurate and ultrafast genomic profiling with exact sequence matches
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-07-03
    Hector F Espitia-Navarro; Aroon T Chande; Shashwat D Nagar; Heather Smith; I King Jordan; Lavanya Rishishwar

    Genome-enabled approaches to molecular epidemiology have become essential to public health agencies and the microbial research community. We developed the algorithm STing to provide turn-key solutions for molecular typing and gene detection directly from next generation sequence data of microbial pathogens. Our implementation of STing uses an innovative k-mer search strategy that eliminates the computational

    更新日期:2020-07-05
  • Poly(A) binding KPAF4/5 complex stabilizes kinetoplast mRNAs in Trypanosoma brucei
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-07-02
    Inna Aphasizheva; Tian Yu; Takuma Suematsu; Qiushi Liu; Mikhail V Mesitov; Clinton Yu; Lan Huang; Liye Zhang; Ruslan Aphasizhev

    In Trypanosoma brucei, mitochondrial pre-mRNAs undergo 3′-5′ exonucleolytic processing, 3′ adenylation and uridylation, 5′ pyrophosphate removal, and, often, U-insertion/deletion editing. The 3′ modifications are modulated by pentatricopeptide repeat (PPR) Kinetoplast Polyadenylation Factors (KPAFs). We have shown that KPAF3 binding to the 3′ region stabilizes properly trimmed transcripts and stimulates

    更新日期:2020-07-02
  • A fully-automated method discovers loss of mouse-lethal and human-monogenic disease genes in 58 mammals
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-07-02
    Yatish Turakhia; Heidi I Chen; Amir Marcovitz; Gill Bejerano

    Gene losses provide an insightful route for studying the morphological and physiological adaptations of species, but their discovery is challenging. Existing genome annotation tools focus on annotating intact genes and do not attempt to distinguish nonfunctional genes from genes missing annotation due to sequencing and assembly artifacts. Previous attempts to annotate gene losses have required significant

    更新日期:2020-07-02
  • Alternative splicing and allosteric regulation modulate the chromatin binding of UHRF1
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-07-01
    Maria Tauber; Sarah Kreuz; Alexander Lemak; Papita Mandal; Zhadyra Yerkesh; Alaguraj Veluchamy; Bothayna Al-Gashgari; Abrar Aljahani; Lorena V Cortés-Medina; Dulat Azhibek; Lixin Fan; Michelle S Ong; Shili Duan; Scott Houliston; Cheryl H Arrowsmith; Wolfgang Fischle

    UHRF1 is an important epigenetic regulator associated with apoptosis and tumour development. It is a multidomain protein that integrates readout of different histone modification states and DNA methylation with enzymatic histone ubiquitylation activity. Emerging evidence indicates that the chromatin-binding and enzymatic modules of UHRF1 do not act in isolation but interplay in a coordinated and regulated

    更新日期:2020-07-01
  • The human box C/D snoRNA U3 is a miRNA source and miR-U3 regulates expression of sortin nexin 27
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-07-01
    Nicolas Lemus-Diaz; Rafael Rinaldi Ferreira; Katherine E Bohnsack; Jens Gruber; Markus T Bohnsack

    MicroRNAs (miRNAs) are important regulators of eukaryotic gene expression and their dysfunction is often associated with cancer. Alongside the canonical miRNA biogenesis pathway involving stepwise processing and export of pri- and pre-miRNA transcripts by the microprocessor complex, Exportin 5 and Dicer, several alternative mechanisms of miRNA production have been described. Here, we reveal that the

    更新日期:2020-07-01
  • Replicative aging is associated with loss of genetic heterogeneity from extrachromosomal circular DNA in Saccharomyces cerevisiae
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-07-01
    Iñigo Prada-Luengo; Henrik D Møller; Rasmus A Henriksen; Qian Gao; Camilla Eggert Larsen; Sefa Alizadeh; Lasse Maretty; Jonathan Houseley; Birgitte Regenberg

    Circular DNA can arise from all parts of eukaryotic chromosomes. In yeast, circular ribosomal DNA (rDNA) accumulates dramatically as cells age, however little is known about the accumulation of other chromosome-derived circles or the contribution of such circles to genetic variation in aged cells. We profiled circular DNA in Saccharomyces cerevisiae populations sampled when young and after extensive

    更新日期:2020-07-01
  • RNA aptamer capture of macromolecular complexes for mass spectrometry analysis
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-07-01
    Judhajeet Ray; Angela Kruse; Abdullah Ozer; Takuya Kajitani; Richard Johnson; Michael MacCoss; Michelle Heck; John T Lis

    Specific genomic functions are dictated by macromolecular complexes (MCs) containing multiple proteins. Affinity purification of these complexes, often using antibodies, followed by mass spectrometry (MS) has revolutionized our ability to identify the composition of MCs. However, conventional immunoprecipitations suffer from contaminating antibody/serum-derived peptides that limit the sensitivity of

    更新日期:2020-07-01
  • Eukaryotic life without tQCUG: the role of Elongator-dependent tRNA modifications in Dictyosteliumdiscoideum
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-07-01
    Manfred A Schäck; Kim Philipp Jablonski; Stefan Gräf; Roland Klassen; Raffael Schaffrath; Stefanie Kellner; Christian Hammann

    In the Elongator-dependent modification pathway, chemical modifications are introduced at the wobble uridines at position 34 in transfer RNAs (tRNAs), which serve to optimize codon translation rates. Here, we show that this three-step modification pathway exists in Dictyostelium discoideum, model of the evolutionary superfamily Amoebozoa. Not only are previously established modifications observable

    更新日期:2020-07-01
  • Processing by RNase 1 forms tRNA halves and distinct Y RNA fragments in the extracellular environment
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-07-01
    Gal Nechooshtan; Dinar Yunusov; Kenneth Chang; Thomas R Gingeras

    Extracellular RNAs participate in intercellular communication, and are being studied as promising minimally invasive diagnostic markers. Several studies in recent years showed that tRNA halves and distinct Y RNA fragments are abundant in the extracellular space, including in biofluids. While their regulatory and diagnostic potential has gained a substantial amount of attention, the biogenesis of these

    更新日期:2020-07-01
  • Binding of a viral IRES to the 40S subunit occurs in two successive steps mediated by eS25
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-07-01
    Beth Walters; Armend Axhemi; Eckhard Jankowsky; Sunnie R Thompson

    The mechanism for how internal ribosome entry sites (IRESs) recruit ribosomes to initiate translation of an mRNA is not completely understood. We investigated how a 40S subunit was recruited by the cricket paralysis virus intergenic region (CrPV IGR) IRES to form a stable 40S–IRES complex. Kinetic binding studies revealed that formation of the complex between the CrPV IGR and the 40S subunit consisted

    更新日期:2020-07-01
  • Toward a translationally independent RNA-based synthetic oscillator using deactivated CRISPR-Cas
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-07-01
    James Kuo; Ruoshi Yuan; Carlos Sánchez; Johan Paulsson; Pamela A Silver

    In synthetic circuits, CRISPR-Cas systems have been used effectively for endpoint changes from an initial state to a final state, such as in logic gates. Here, we use deactivated Cas9 (dCas9) and deactivated Cas12a (dCas12a) to construct dynamic RNA ring oscillators that cycle continuously between states over time in bacterial cells. While our dCas9 circuits using 103-nt guide RNAs showed irregular

    更新日期:2020-07-01
  • DSS1 and ssDNA regulate oligomerization of BRCA2
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-07-01
    Hang Phuong Le; Xiaoyan Ma; Jorge Vaquero; Megan Brinkmeyer; Fei Guo; Wolf-Dietrich Heyer; Jie Liu

    The tumor suppressor BRCA2 plays a key role in initiating homologous recombination by facilitating RAD51 filament formation on single-stranded DNA. The small acidic protein DSS1 is a crucial partner to BRCA2 in this process. In vitro and in cells (1,2), BRCA2 associates into oligomeric complexes besides also existing as monomers. A dimeric structure was further characterized by electron microscopic

    更新日期:2020-07-01
  • MicroRNA dilution during oocyte growth disables the microRNA pathway in mammalian oocytes
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-07-01
    Shubhangini Kataruka; Martin Modrak; Veronika Kinterova; Radek Malik; Daniela M Zeitler; Filip Horvat; Jiri Kanka; Gunter Meister; Petr Svoboda

    MicroRNAs (miRNAs) are ubiquitous small RNAs guiding post-transcriptional gene repression in countless biological processes. However, the miRNA pathway in mouse oocytes appears inactive and dispensable for development. We propose that marginalization of the miRNA pathway activity stems from the constraints and adaptations of RNA metabolism elicited by the diluting effects of oocyte growth. We report

    更新日期:2020-07-01
  • Fragment-based discovery of a new class of inhibitors targeting mycobacterial tRNA modification
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-06-30
    Sherine E Thomas; Andrew J Whitehouse; Karen Brown; Sophie Burbaud; Juan M Belardinelli; Jasper Sangen; Ramanuj Lahiri; Mark Daben J Libardo; Pooja Gupta; Sony Malhotra; Helena I M Boshoff; Mary Jackson; Chris Abell; Anthony G Coyne; Tom L Blundell; Rodrigo Andres Floto; Vítor Mendes

    Translational frameshift errors are often deleterious to the synthesis of functional proteins and could therefore be promoted therapeutically to kill bacteria. TrmD (tRNA-(N(1)G37) methyltransferase) is an essential tRNA modification enzyme in bacteria that prevents +1 errors in the reading frame during protein translation and represents an attractive potential target for the development of new antibiotics

    更新日期:2020-06-30
  • The chromatin landscape at the HIV-1 provirus integration site determines viral expression
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-06-29
    Gerlinde Vansant; Heng-Chang Chen; Eduard Zorita; Katerina Trejbalová; Dalibor Miklík; Guillaume Filion; Zeger Debyser

    HIV-1 persists lifelong in memory cells of the immune system as latent provirus that rebounds upon treatment interruption. Therefore, the latent reservoir is the main target for an HIV cure. Here, we studied the direct link between integration site and transcription using LEDGINs and Barcoded HIV-ensembles (B-HIVE). LEDGINs are antivirals that inhibit the interaction between HIV-1 integrase and the

    更新日期:2020-06-29
  • A unified view of the sequence and functional organization of the human RNA polymerase II promoter
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-06-29
    Donal S Luse; Mrutyunjaya Parida; Benjamin M Spector; Kyle A Nilson; David H Price

    To better understand human RNA polymerase II (Pol II) promoters in the context of promoter-proximal pausing and local chromatin organization, 5′ and 3′ ends of nascent capped transcripts and the locations of nearby nucleosomes were accurately identified through sequencing at exceptional depth. High-quality visualization tools revealed a preferred sequence that defines over 177 000 core promoters with

    更新日期:2020-06-29
  • The structural ensemble of a Holliday junction determined by X-ray scattering interference
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-06-29
    Thomas Zettl; Xuesong Shi; Steve Bonilla; Steffen M Sedlak; Jan Lipfert; Daniel Herschlag

    The DNA four-way (Holliday) junction is the central intermediate of genetic recombination, yet key aspects of its conformational and thermodynamic properties remain unclear. While multiple experimental approaches have been used to characterize the canonical X-shape conformers under specific ionic conditions, the complete conformational ensemble of this motif, especially at low ionic conditions, remains

    更新日期:2020-06-29
  • Analysis of a preQ1-I riboswitch in effector-free and bound states reveals a metabolite-programmed nucleobase-stacking spine that controls gene regulation
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-06-29
    Griffin M Schroeder; Debapratim Dutta; Chapin E Cavender; Jermaine L Jenkins; Elizabeth M Pritchett; Cameron D Baker; John M Ashton; David H Mathews; Joseph E Wedekind

    Riboswitches are structured RNA motifs that recognize metabolites to alter the conformations of downstream sequences, leading to gene regulation. To investigate this molecular framework, we determined crystal structures of a preQ1-I riboswitch in effector-free and bound states at 2.00 Å and 2.65 Å-resolution. Both pseudoknots exhibited the elusive L2 loop, which displayed distinct conformations. Conversely

    更新日期:2020-06-29
  • Small-molecule sensitization of RecBCD helicase–nuclease to a Chi hotspot-activated state
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-06-29
    Ahmet C Karabulut; Ryan T Cirz; Andrew F Taylor; Gerald R Smith

    Coordinating multiple activities of complex enzymes is critical for life, including transcribing, replicating and repairing DNA. Bacterial RecBCD helicase–nuclease must coordinate DNA unwinding and cutting to repair broken DNA. Starting at a DNA end, RecBCD unwinds DNA with its fast RecD helicase on the 5′-ended strand and its slower RecB helicase on the 3′-ended strand. At Chi hotspots (5′ GCTGGTGG

    更新日期:2020-06-29
  • Mechanism of translation inhibition by type II GNAT toxin AtaT2
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-06-29
    Stepan V Ovchinnikov; Dmitry Bikmetov; Alexei Livenskyi; Marina Serebryakova; Brendan Wilcox; Kyle Mangano; Dmitrii I Shiriaev; Ilya A Osterman; Petr V Sergiev; Sergei Borukhov; Nora Vazquez-Laslop; Alexander S Mankin; Konstantin Severinov; Svetlana Dubiley

    Type II toxin–antitoxins systems are widespread in prokaryotic genomes. Typically, they comprise two proteins, a toxin, and an antitoxin, encoded by adjacent genes and forming a complex in which the enzymatic activity of the toxin is inhibited. Under stress conditions, the antitoxin is degraded liberating the active toxin. Though thousands of various toxin–antitoxins pairs have been predicted bioinformatically

    更新日期:2020-06-29
  • Asymmetric dimerization of adenosine deaminase acting on RNA facilitates substrate recognition
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-06-29
    Alexander S Thuy-Boun; Justin M Thomas; Herra L Grajo; Cody M Palumbo; SeHee Park; Luan T Nguyen; Andrew J Fisher; Peter A Beal

    Adenosine deaminases acting on RNA (ADARs) are enzymes that convert adenosine to inosine in duplex RNA, a modification that exhibits a multitude of effects on RNA structure and function. Recent studies have identified ADAR1 as a potential cancer therapeutic target. ADARs are also important in the development of directed RNA editing therapeutics. A comprehensive understanding of the molecular mechanism

    更新日期:2020-06-29
  • The methyltransferase TrmA facilitates tRNA folding through interaction with its RNA-binding domain
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-06-29
    Laura Carole Keffer-Wilkes; Emily F Soon; Ute Kothe

    tRNAs are the most highly modified RNAs in all cells, and formation of 5-methyluridine (m5U) at position 54 in the T arm is a common RNA modification found in all tRNAs. The m5U modification is generated by the methyltransferase TrmA. Here, we test and prove the hypothesis that Escherichia coli TrmA has dual functions, acting both as a methyltransferase and as a tRNA chaperone. We identify two conserved

    更新日期:2020-06-29
  • Editorial: the 18th annual Nucleic Acids Research web server issue 2020
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-06-21

    The 2020 version of Nucleic Acids Research's web server issue marks a change. This 18th web server issue is the first one to be assembled without the editorial supervision of Gary Benson, who served as its executive editor for more than a decade and whose work has made the issue the most prominent resource for scientific web-based applications.

    更新日期:2020-06-27
  • RNAProbe: a web server for normalization and analysis of RNA structure probing data.
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-06-06
    Tomasz K Wirecki,Katarzyna Merdas,Agata Bernat,Michał J Boniecki,Janusz M Bujnicki,Filip Stefaniak

    RNA molecules play key roles in all living cells. Knowledge of the structural characteristics of RNA molecules allows for a better understanding of the mechanisms of their action. RNA chemical probing allows us to study the susceptibility of nucleotides to chemical modification, and the information obtained can be used to guide secondary structure prediction. These experimental results can be analyzed

    更新日期:2020-06-27
  • SNPnexus: a web server for functional annotation of human genome sequence variation (2020 update).
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-06-04
    Jorge Oscanoa,Lavanya Sivapalan,Emanuela Gadaleta,Abu Z Dayem Ullah,Nicholas R Lemoine,Claude Chelala

    SNPnexus is a web-based annotation tool for the analysis and interpretation of both known and novel sequencing variations. Since its last release, SNPnexus has received continual updates to expand the range and depth of annotations provided. SNPnexus has undergone a complete overhaul of the underlying infrastructure to accommodate faster computational times. The scope for data annotation has been substantially

    更新日期:2020-06-27
  • Tox21BodyMap: a webtool to map chemical effects on the human body.
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-06-03
    Alexandre Borrel,Scott S Auerbach,Keith A Houck,Nicole C Kleinstreuer

    To support rapid chemical toxicity assessment and mechanistic hypothesis generation, here we present an intuitive webtool allowing a user to identify target organs in the human body where a substance is estimated to be more likely to produce effects. This tool, called Tox21BodyMap, incorporates results of 9,270 chemicals tested in the United States federal Tox21 research consortium in 971 high-throughput

    更新日期:2020-06-27
  • miRNet 2.0: network-based visual analytics for miRNA functional analysis and systems biology.
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-06-02
    Le Chang,Guangyan Zhou,Othman Soufan,Jianguo Xia

    miRNet is an easy-to-use, web-based platform designed to help elucidate microRNA (miRNA) functions by integrating users' data with existing knowledge via network-based visual analytics. Since its first release in 2016, miRNet has been accessed by >20 000 researchers worldwide, with ∼100 users on a daily basis. While version 1.0 was focused primarily on miRNA-target gene interactions, it has become

    更新日期:2020-06-27
  • HomolWat: a web server tool to incorporate 'homologous' water molecules into GPCR structures.
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-06-02
    Eduardo Mayol,Adrián García-Recio,Johanna K S Tiemann,Peter W Hildebrand,Ramon Guixà-González,Mireia Olivella,Arnau Cordomí

    Internal water molecules play an essential role in the structure and function of membrane proteins including G protein-coupled receptors (GPCRs). However, technical limitations severely influence the number and certainty of observed water molecules in 3D structures. This may compromise the accuracy of further structural studies such as docking calculations or molecular dynamics simulations. Here we

    更新日期:2020-06-27
  • mirnaQC: a webserver for comparative quality control of miRNA-seq data.
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-06-02
    Ernesto Aparicio-Puerta,Cristina Gómez-Martín,Stavros Giannoukakos,José María Medina,Juan Antonio Marchal,Michael Hackenberg

    Although miRNA-seq is extensively used in many different fields, its quality control is frequently restricted to a PhredScore-based filter. Other important quality related aspects like microRNA yield, the fraction of putative degradation products (such as rRNA fragments) or the percentage of adapter-dimers are hard to assess using absolute thresholds. Here we present mirnaQC, a webserver that relies

    更新日期:2020-06-27
  • CReSCENT: CanceR Single Cell ExpressioN Toolkit.
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-06-01
    Suluxan Mohanraj,J Javier Díaz-Mejía,Martin D Pham,Hillary Elrick,Mia Husić,Shaikh Rashid,Ping Luo,Prabnur Bal,Kevin Lu,Samarth Patel,Alaina Mahalanabis,Alaine Naidas,Erik Christensen,Danielle Croucher,Laura M Richards,Parisa Shooshtari,Michael Brudno,Arun K Ramani,Trevor J Pugh

    CReSCENT: CanceR Single Cell ExpressioN Toolkit (https://crescent.cloud), is an intuitive and scalable web portal incorporating a containerized pipeline execution engine for standardized analysis of single-cell RNA sequencing (scRNA-seq) data. While scRNA-seq data for tumour specimens are readily generated, subsequent analysis requires high-performance computing infrastructure and user expertise to

    更新日期:2020-06-27
  • The Galaxy platform for accessible, reproducible and collaborative biomedical analyses: 2020 update.
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-06-01
    Vahid Jalili,Enis Afgan,Qiang Gu,Dave Clements,Daniel Blankenberg,Jeremy Goecks,James Taylor,Anton Nekrutenko

    Galaxy (https://galaxyproject.org) is a web-based computational workbench used by tens of thousands of scientists across the world to analyze large biomedical datasets. Since 2005, the Galaxy project has fostered a global community focused on achieving accessible, reproducible, and collaborative research. Together, this community develops the Galaxy software framework, integrates analysis tools and

    更新日期:2020-06-27
  • TopMatch-web: pairwise matching of large assemblies of protein and nucleic acid chains in 3D.
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-06-01
    Markus Wiederstein,Manfred J Sippl

    Frequently, the complete functional units of biological molecules are assemblies of protein and nucleic acid chains. Stunning examples are the complex structures of ribosomes. Here, we present TopMatch-web, a computational tool for the study of the three-dimensional structure, function and evolution of such molecules. The unique feature of TopMatch is its ability to match the protein as well as nucleic

    更新日期:2020-06-27
  • FATCAT 2.0: towards a better understanding of the structural diversity of proteins.
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-05-29
    Zhanwen Li,Lukasz Jaroszewski,Mallika Iyer,Mayya Sedova,Adam Godzik

    FATCAT 2.0 server (http://fatcat.godziklab.org/), provides access to a flexible protein structure alignment algorithm developed in our group. In such an alignment, rotations and translations between elements in the structure are allowed to minimize the overall root mean square deviation (RMSD) between the compared structures. This allows to effectively compare protein structures even if they underwent

    更新日期:2020-06-27
  • mCSM-membrane: predicting the effects of mutations on transmembrane proteins.
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-05-29
    Douglas E V Pires,Carlos H M Rodrigues,David B Ascher

    Significant efforts have been invested into understanding and predicting the molecular consequences of mutations in protein coding regions, however nearly all approaches have been developed using globular, soluble proteins. These methods have been shown to poorly translate to studying the effects of mutations in membrane proteins. To fill this gap, here we report, mCSM-membrane, a user-friendly web

    更新日期:2020-06-27
  • piNET: a versatile web platform for downstream analysis and visualization of proteomics data.
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-05-29
    Behrouz Shamsaei,Szymon Chojnacki,Marcin Pilarczyk,Mehdi Najafabadi,Wen Niu,Chuming Chen,Karen Ross,Andrea Matlock,Jeremy Muhlich,Somchai Chutipongtanate,Jie Zheng,John Turner,Dušica Vidović,Jake Jaffe,Michael MacCoss,Cathy Wu,Ajay Pillai,Avi Ma'ayan,Stephan Schürer,Michal Kouril,Mario Medvedovic,Jarek Meller

    Rapid progress in proteomics and large-scale profiling of biological systems at the protein level necessitates the continued development of efficient computational tools for the analysis and interpretation of proteomics data. Here, we present the piNET server that facilitates integrated annotation, analysis and visualization of quantitative proteomics data, with emphasis on PTM networks and integration

    更新日期:2020-06-27
  • PaCRISPR: a server for predicting and visualizing anti-CRISPR proteins.
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-05-27
    Jiawei Wang,Wei Dai,Jiahui Li,Ruopeng Xie,Rhys A Dunstan,Christopher Stubenrauch,Yanju Zhang,Trevor Lithgow

    Anti-CRISPRs are widespread amongst bacteriophage and promote bacteriophage infection by inactivating the bacterial host's CRISPR–Cas defence system. Identifying and characterizing anti-CRISPR proteins opens an avenue to explore and control CRISPR–Cas machineries for the development of new CRISPR–Cas based biotechnological and therapeutic tools. Past studies have identified anti-CRISPRs in several

    更新日期:2020-06-27
  • ShiftCrypt: a web server to understand and biophysically align proteins through their NMR chemical shift values.
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-05-27
    Gabriele Orlando,Daniele Raimondi,Luciano Porto Kagami,Wim F Vranken

    Nuclear magnetic resonance (NMR) spectroscopy data provides valuable information on the behaviour of proteins in solution. The primary data to determine when studying proteins are the per-atom NMR chemical shifts, which reflect the local environment of atoms and provide insights into amino acid residue dynamics and conformation. Within an amino acid residue, chemical shifts present multi-dimensional

    更新日期:2020-06-27
  • EpiRegio: analysis and retrieval of regulatory elements linked to genes.
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-05-27
    Nina Baumgarten,Dennis Hecker,Sivarajan Karunanithi,Florian Schmidt,Markus List,Marcel H Schulz

    A current challenge in genomics is to interpret non-coding regions and their role in transcriptional regulation of possibly distant target genes. Genome-wide association studies show that a large part of genomic variants are found in those non-coding regions, but their mechanisms of gene regulation are often unknown. An additional challenge is to reliably identify the target genes of the regulatory

    更新日期:2020-06-27
  • CVCDAP: an integrated platform for molecular and clinical analysis of cancer virtual cohorts.
    Nucleic Acids Res. (IF 11.501) Pub Date : 2020-05-25
    Xiaoqing Guan,Meng Cai,Yang Du,Ence Yang,Jiafu Ji,Jianmin Wu

    Recent large-scale multi-omics studies resulted in quick accumulation of an overwhelming amount of cancer-related data, which provides an unprecedented resource to interrogate diverse questions. While certain existing web servers are valuable and widely used, analysis and visualization functions with regard to re-investigation of these data at cohort level are not adequately addressed. Here, we present

    更新日期:2020-06-27
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