Molecular biology articles within Nature Communications

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  • Article
    | Open Access

    The gut microbiota can impact the bioavailability of therapeutic drugs. Here, the authors show that bacterial tyrosine decarboxylases (TDC) decrease the levels of levodopa, the primary treatment in Parkinson’s disease, by conversion to dopamine, and suggest TDC as a potential predictive biomarker for treatment.

    • Sebastiaan P. van Kessel
    • , Alexandra K. Frye
    •  & Sahar El Aidy

  • Article
    | Open Access

    Hydra regenerate various body parts on amputation by activation of the appropriate organiser, but how head formation is controlled is unclear. Here, the authors identify the transcription factor Sp5 as restricting head formation, by being activated by beta-catenin and then acting as a repressor of Wnt3.

    • Matthias C. Vogg
    • , Leonardo Beccari
    •  & Brigitte Galliot

  • Article
    | Open Access

    During cell division, faithful chromosome segregation requires proper chromosome congression and dynamic maintenance of the aligned chromosomes. Here, the authors find that LUBAC promotes dynamic chromosome congression and alignment by targeting kinetochore motor CENP-E to the KMN network.

    • Min Wu
    • , Yan Chang
    •  & Huiyan Li

  • Article
    | Open Access

    Overexpression of RAS proteins is frequently observed in patients with hepatocellular carcinoma. Here, the authors identify an HRAS binding protein, the E3 ubiquitin ligase WDR76, which promotes HRAS degradation, thus functioning as a tumour suppressor in liver cancer

    • Woo-Jeong Jeong
    • , Jong-Chan Park
    •  & Kang-Yell Choi

  • Article
    | Open Access

    In fission yeast, Erh1, ortholog of human ERH, interacts with the YTH family RNA binding protein Mmi1 to form the Erh1-Mmi1 complex (EMC), which has been implicated in gene silencing. Here, the authors present the cocrystal structure of Erh1 homodimers interacting with Mmi1 and further characterise the role of EMC in facultative heterochromatin assembly and gene silencing.

    • Guodong Xie
    • , Tommy V. Vo
    •  & Shiv I. S. Grewal

  • Article
    | Open Access

    Oxidative DNA damage is associated with nucleosome respacing and transcriptional changes requiring chromatin remodeling enzymes. Here, the authors reveal that the CHD6 remodeler is a DNA damage response factor that relocates to damaged sites and promotes cell survival following oxidative damage.

    • Shaun Moore
    • , N. Daniel Berger
    •  & Aaron A. Goodarzi

  • Article
    | Open Access

    Animal studies have shown that the nutritional status of parents can predispose the offspring to obesity and obesity-related diseases. Here the authors show that cardiac dysfunction induced by a high-fat diet persists for two generations in Drosophila, and that targeted expression of ATGL/bmm in the offspring, as well as inhibition of H3K27 trimethylation, is cardioprotective.

    • Maria Clara Guida
    • , Ryan Tyge Birse
    •  & Rolf Bodmer

  • Article
    | Open Access

    Polyadenylation stabilizes edited mitochondrial mRNAs in Trypanosoma brucei, but the involved poly(A) binding protein is unknown. Here, Mesitov et al. show that a pentatricopeptide repeat factor KPAF4 binds to A-tail and prevents exonucleolytic degradation as well as translation of incompletely edited mRNAs.

    • Mikhail V. Mesitov
    • , Tian Yu
    •  & Inna Aphasizheva

  • Article
    | Open Access

    Phosphorylation of CENP-A on serine 7 has been proposed to control centromere assembly and function. Here, the authors use gene targeting at both endogenous CENP-A alleles and gene replacement in human cells to demonstrate that CENP-A that cannot be phosphorylated at serine 7 maintains correct CENP-C recruitment, faithful chromosome segregation and long-term cell viability.

    • Viviana Barra
    • , Glennis A. Logsdon
    •  & Daniele Fachinetti

  • Article
    | Open Access

    Splicing factors are often mutated in hematological malignancies. Here, the authors perform an in vivo shRNA screen in a CEBPA mutant AML mouse model and identify that RBM25 controls the splicing of pre-mRNAs encoding BCL-X and BIN1 to exert its tumour suppressor activities in AML.

    • Ying Ge
    • , Mikkel Bruhn Schuster
    •  & Bo Torben Porse

  • Article
    | Open Access

    The authors perform single-cell RNA-seq of the mouse neocortex at an embryonic time point and at birth, and identify new and known cell types, and cell relatedness within and across age. These data serve as a resource to understand brain development and the cellular origins of brain diseases.

    • Lipin Loo
    • , Jeremy M. Simon
    •  & Mark J. Zylka

  • Article
    | Open Access

    Trypanosoma brucei mainly relies on translational regulation to adjust gene expression, but details are unclear. Here the authors show that, under stress conditions, tRNAThr half level increases, associates with ribosomes and polysomes, and stimulates protein synthesis by facilitating mRNA loading.

    • Roger Fricker
    • , Rebecca Brogli
    •  & Norbert Polacek

  • Article
    | Open Access

    The human genome includes a large amount of repetitive sequence, such as human satellite II (HSATII), but their function remains largely unknown. Here, Nogalski et al. show that herpesvirus infection induces HSATII RNA expression, which in turn affects virus replication and cell motility.

    • Maciej T. Nogalski
    • , Alexander Solovyov
    •  & Benjamin D. Greenbaum

  • Article
    | Open Access

    The demethylase activity of KDM5A is allosterically enhanced by binding of histone H3 to its PHD1 reader domain, through an unknown mechanism. Here the authors show that the PHD1 domain drives ligand-induced allosteric stimulation by stabilizing the binding of substrate to the catalytic domain.

    • James E. Longbotham
    • , Cynthia M. Chio
    •  & Danica Galonić Fujimori

  • Article
    | Open Access

    The inactive X chromosome (Xi) has an atypical structure, with global loss of TADs, A/B compartments and formation of mega-domains. Here the authors show that the non-canonical SMC family protein, SmcHD1, important for developmental gene silencing on Xi, antagonises TAD formation and compartmentalization on the Xi in a transcription independent way.

    • Michal R. Gdula
    • , Tatyana B. Nesterova
    •  & Neil Brockdorff

  • Article
    | Open Access

    MLL3 and MLL4 are members of the SET1/MLL family of histone H3K4 methyltransferases, which are responsible for monomethylating histone H3K4 on enhancers. Here the authors show that an extended PHD domain (ePHD6) in MLL3 and MLL4 specifically recognizes an H4H18-containing fragment of histone H4, and that modifications of residues surrounding H4H18 modulate H4 binding to MLL3/4.

    • Yanli Liu
    • , Su Qin
    •  & Jinrong Min

  • Article
    | Open Access

    The human stomach is divided into seven anatomically distinct regions but their protein composition is largely unknown. Here, the authors present a region-resolved map of the healthy human stomach mucosa as well as mucosa proteomes of tumor and tumor nearby tissue from gastric cancer patients.

    • Xiaotian Ni
    • , Zhaoli Tan
    •  & Jun Qin

  • Article
    | Open Access

    Protein methyltransferases (PMTs) are epigenetic regulatory enzymes with significant therapeutic relevance. Here the authors describe a collection of chemical inhibitors and antagonists to modulate most of the key methylation marks on histones H3 and H4, and use the collection to study of the role of PMTs in mouse and human T cell differentiation.

    • Sebastian Scheer
    • , Suzanne Ackloo
    •  & Cheryl H. Arrowsmith

  • Article
    | Open Access

    Eukaryotic transcription requires passage of RNA polymerase II (Pol II) through chromatin, which is impaired by nucleosomes. Here the authors report the cryo-EM structure of transcribing Pol II engaged with a downstream nucleosome core particle at an overall resolution of 4.4 Å, providing insights into the mechanism of chromatin transcription.

    • Lucas Farnung
    • , Seychelle M. Vos
    •  & Patrick Cramer

  • Article
    | Open Access

    Substrate reduction therapies (SRT) are a promising therapeutic approach for monogenic inherited metabolic diseases. Here the authors evaluate the therapeutic potential of an in vivo CRISPR/Cas9-mediated SRT to treat primary hyperoxaluria type I and demonstrate its safety and efficacy.

    • Nerea Zabaleta
    • , Miren Barberia
    •  & Juan R. Rodriguez-Madoz

  • Article
    | Open Access

    Quantification of genomic responses to environmental stimuli by current genome-scale assays is limited to indirect measurements or requires knowledge of the transcription factors involved. Here, the authors use genome-wide high-throughput reporter assays to agnostically map enhancer activity in response to glucocorticoid treatment across the human genome.

    • Graham D. Johnson
    • , Alejandro Barrera
    •  & Timothy E. Reddy

  • Article
    | Open Access

    Genome-wide libraries for CRISPR knockout, interference, and activation have allowed the systemic interrogation of gene function. Here, the authors evaluate the Brunello CRISPRko library and introduce Dolcetto and Calabrese for CRISPRi and CRISPRa, respectively.

    • Kendall R. Sanson
    • , Ruth E. Hanna
    •  & John G. Doench

  • Article
    | Open Access

    Transient aneuploidy enables cells to survive sudden environmental changes before longterm cellular adaptations are established. Here, the authors show that yeast cells respond to the acute loss of Ulp2 SUMO protease by rapid induction of aneuploidy, and reveal predictable long-term adaptation mechanisms that restore euploidy.

    • Hong-Yeoul Ryu
    • , Francesc López-Giráldez
    •  & Mark Hochstrasser

  • Article
    | Open Access

    How DNA repair proteins locate their target sites on DNA is still a matter of debate. Here the authors characterize by single-molecule fluorescence imaging the modes of scanning adopted by bacterial endonuclease V as it moves along linear DNA tracks.

    • Arash Ahmadi
    • , Ida Rosnes
    •  & Alexander D. Rowe

  • Article
    | Open Access

    Pre-ribosomes undergo numerous structural rearrangements during their assembly. Here the authors identify the binding sites of three essential RNA helicases on pre-ribosomal particles, enabling them to provide insights into the structural and compositional changes that occur during biogenesis of the large ribosomal subunit.

    • Lukas Brüning
    • , Philipp Hackert
    •  & Markus T. Bohnsack

  • Article
    | Open Access

    ATR kinase is a key regulator of chromosome integrity. Here the authors by analysing the phenotype of a mouse model expressing a kinase-dead ATR, reveal the effect of ATR inhibition compared to ATR loss and its consequences for meiosis, DNA replication, checkpoint activation and genome instability .

    • Demis Menolfi
    • , Wenxia Jiang
    •  & Shan Zha

  • Article
    | Open Access

    BAG3 is a Hsp70 co-chaperone that is highly expressed in muscles. Here the authors show that several myofibrillar myopathy causing BAG3 mutations are not impaired in Hsp70 binding, but rather impair the ADP-ATP exchange step of the Hsp70 cycle, causing the aggregation of BAG3, Hsp70 and Hsp70 clients and leading to a collapse of protein homeostasis.

    • Melanie Meister-Broekema
    • , Rebecca Freilich
    •  & Harm H. Kampinga

  • Article
    | Open Access

    The mechanisms of ZIKV persistence in the male reproductive tract (MRT) are poorly understood. Here, Tsetsarkin et al. applied microRNA-targeting approach to trace routes of ZIKV dissemination in the testis and epididymis and to generate immunogenic live-attenuated ZIKV vaccine candidate, restricted for MRT infection.

    • Konstantin A. Tsetsarkin
    • , Olga A. Maximova
    •  & Alexander G. Pletnev

  • Article
    | Open Access

    Increasing insecticide resistance of mosquitoes represents a public health threat, and underlying mechanisms are poorly understood. Here, Ingham et al. identify putative insecticide resistance genes in Anopheles gambiae populations across Africa and develop a web-based application that maps their expression.

    • V. A. Ingham
    • , S. Wagstaff
    •  & H. Ranson

  • Article
    | Open Access

    HMGN1 and HMGN2 are ubiquitous nucleosome binding proteins. Here the authors provide evidence that HMGN proteins preferentially localize to chromatin regulatory sites to modulate the plasticity of the epigenetic landscape, proposing that HGMNs stabilize, rather than determine, cell identity.

    • Bing He
    • , Tao Deng
    •  & Michael Bustin

  • Article
    | Open Access

    Myotonic dystrophy type 1 (DM1) is associated with aberrant transcript splicing. Here, the authors develop a transgenic mouse model expressing a bi-chromatic reporter system that allows non-invasive monitoring of splicing of a transcript altered in DM1 in vivo, and show that it allows for evaluation of the therapeutic response to treatment with antisense oligonucleotides.

    • Ningyan Hu
    • , Layal Antoury
    •  & Thurman M. Wheeler

  • Article
    | Open Access

    Zelda is a pioneer factor that regulates transcription in Drosophila embryos. Here, the authors use quantitative live imaging and mathematical modeling to measure the effect of Zelda on transcriptional dynamics and memory, observing temporal control of gene expression by Zelda through transient interactions in hubs.

    • Jeremy Dufourt
    • , Antonio Trullo
    •  & Mounia Lagha

  • Article
    | Open Access

    Multimorbidities of common diseases often have shared underlying predisposing factors. Here Fadason et al. study the pleiotropy of SNPs and their effects on target genes by integrating chromatin interaction and expression quantitative trait loci data to identify target genes shared between phenotypes.

    • Tayaza Fadason
    • , William Schierding
    •  & Justin M. O’Sullivan

  • Review Article
    | Open Access

    In this review, Aravin and colleagues examine bacterial and archaeal Argonaute proteins, discuss their diverse architectures and their possible roles in host defense, proposing additional functions for Argonaute proteins in prokaryotic cells.

    • Lidiya Lisitskaya
    • , Alexei A. Aravin
    •  & Andrey Kulbachinskiy

  • Article
    | Open Access

    Royal jelly is the queen-maker for the honey bee that also has effects on longevity, fertility, and regeneration in mammals. Here the authors provide evidence that its major protein component Royalactin, and the mammalian structural analog Regina, maintain pluripotency in mouse ESCs by activating a ground-state pluripotency-like gene network.

    • Derrick C. Wan
    • , Stefanie L. Morgan
    •  & Kevin C. Wang

  • Article
    | Open Access

    DNA methylation is an epigenetic modification that control genetic programs. Here, the authors found that the methylation landscape influences the physicochemical properties of DNA and that it can serve as a universal cancer biomarker, and developed a one-step assay for the detection of cancer DNA.

    • Abu Ali Ibn Sina
    • , Laura G. Carrascosa
    •  & Matt Trau

  • Article
    | Open Access

    The histone variant macroH2A1 localizes to two functionally distinct chromatin subtypes marked by either H3K27me3 or H2B acetylations. Here the authors identify the features of macroH2A1 required for its recruitment to H2B-acetylated chromatin and identify H2BK20 acetylation as a critical requirement for this recruitment.

    • Penelope D. Ruiz
    •  & Matthew J. Gamble

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