Molecular biology articles within Nature Communications

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  • Article
    | Open Access

    The mechanisms that regulate the activity of Ca2 +/calmodulin-dependent protein kinase II (CaMKII) in the context of heart failure are incompletely understood. Here the authors show that protein arginine methyltransferase 1 (PRMT1) prevents cardiac hyperactivation of CaMKII and heart failure development by methylating CaMKII at arginine residues 9 and 275.

    • Jung-Hoon Pyun
    • , Hyun-Ji Kim
    •  & Jong-Sun Kang

  • Article
    | Open Access

    Eukaryotic origin firing depends on assembly of the Cdc45-MCM-GINS (CMG) helicase, which requires the leading-strand polymerase Pol ɛ. Here the authors present a structural analysis of a CMG Pol ɛ on a DNA fork, providing insight on the steps leading productive helicase engagement to the DNA junction.

    • Panchali Goswami
    • , Ferdos Abid Ali
    •  & Alessandro Costa

  • Article
    | Open Access

    The helical transmembrane segments of membrane proteins play central roles in sensory transduction but the mechanistic basis for their function remains unresolved. Here the authors identify regions in the S4 voltage-sensing segment of Shaker potassium channels where local helical structure is reliant upon backbone amide support.

    • Daniel T. Infield
    • , Kimberly Matulef
    •  & Francis I. Valiyaveetil

  • Article
    | Open Access

    Artificial genetic polymers (XNAs) have been explored for their nuclease activity, but XNAzymes have proven challenging to discover by in vitro selection. Here, the authors generate an efficient RNA-cleaving 2’-fluoroarabino nucleic acid enzyme (FANAzyme) by in vitro evolution using natural DNA polymerases.

    • Yajun Wang
    • , Arlene K. Ngor
    •  & John C. Chaput

  • Article
    | Open Access

    Chromatin conformation studies are limited by the large amounts of starting material required to perform current protocols. Here the authors present Low-C, a Hi-C method for low amounts of input material and produce Low-C maps from primary B-cells of a diffuse large B-cell lymphoma patient, demonstrating the suitability of Low-C to analyse rare cell populations.

    • Noelia Díaz
    • , Kai Kruse
    •  & Juan M. Vaquerizas

  • Article
    | Open Access

    Complex RNA three-dimensional structures undergo functionally important programmed conformational changes. Here, the authors report how two structurally and functionally coupled RNA domains within a viral 3′-UTR sense the ribosome through conformational changes and respond by modulating translation.

    • Erik W. Hartwick
    • , David A. Costantino
    •  & Jeffrey S. Kieft

  • Article
    | Open Access

    Myoblast fusion in skeletal muscle is a complex process but how this is regulated is unclear. Here, the authors identify Ash1L, a histone methyltransferase, as modulating myoblast fusion via activation of the myogenesis gene Cdon, and observe decreased Ash1L expression in Duchenne muscular dystrophy.

    • Ilaria Castiglioni
    • , Roberta Caccia
    •  & Davide Gabellini

  • Article
    | Open Access

    The mammalian inactive X-chromosome (Xi) is organized into megadomains and superloops directed by the noncoding loci, Dxz4 and Firre. Here the authors provide evidence that megadomains do not precede Xist expression or Xi gene silencing, and suggest that Dxz4, Firre, and megadomains are dispensable for Xi silencing and escape from X-inactivation.

    • John E. Froberg
    • , Stefan F. Pinter
    •  & Jeannie T. Lee

  • Article
    | Open Access

    TRIM24 is stabilized in SPOP-mutated prostate cancers, but the regulation of TRIM24 in wild-type prostate cancers is unknown. Here, the authors show that TRIM28 interacts with TRIM24 to prevent SPOP-mediated ubiquitination of TRIM24 and enhances TRIM24 and AR signaling to induce prostate cancer tumorigenesis.

    • Ka-wing Fong
    • , Jonathan C. Zhao
    •  & Jindan Yu

  • Article
    | Open Access

    Proteome and transcriptome often show poor correlation, hindering the system-wide analysis of post-transcriptional regulation. Here, the authors study proteome and transcriptome dynamics during Drosophila embryogenesis and present basic mathematical models describing the temporal regulation of most protein-RNA pairs.

    • Kolja Becker
    • , Alina Bluhm
    •  & Stefan Legewie

  • Article
    | Open Access

    The dynamics of biomolecules can occur over a wide range of time and length scales. Here the authors develop a high-speed AFM height spectroscopy method to directly detect the motion of unlabeled molecules at Angstrom spatial and microsecond temporal resolution.

    • George R. Heath
    •  & Simon Scheuring

  • Article
    | Open Access

    The dynamics of protein acetylation during infection remains unexplored. Here, Murray et al. characterize spatio-temporal acetylations of both cellular and viral proteins during HCMV infection, providing new functional insights into the host-virus acetylome that might help identify new antiviral targets.

    • L. A. Murray
    • , X. Sheng
    •  & I. M. Cristea

  • Article
    | Open Access

    Topoisomerases solve topological problems during DNA metabolism, but their role in RNA metabolism remains unclear. Here the authors provide evidence that in Drosophila, Topoisomerase 3β interacts biochemically and genetically with the RNAi-induced silencing complex (RISC) to promote heterochromatin formation and transcriptional silencing.

    • Seung Kyu Lee
    • , Yutong Xue
    •  & Weidong Wang

  • Article
    | Open Access

    Artificial gene circuits represent intellectual property that under some circumstances may need to be obfuscated to prevent discovery by third parties. Here the authors use encryption by overlapping recombinase sites and steganography by the introduction of superfluous components, to obscure circuit topology.

    • Oliver Purcell
    • , Jerry Wang
    •  & Timothy K. Lu

  • Article
    | Open Access

    The mammalian stomach is a complex organ with diverse roles in health and disease. Here, the authors integrate proteomics and transcriptomics to analyze the mouse stomach at 15 time points during development, providing molecular level insights into system-wide developmental changes.

    • Xianju Li
    • , Chunchao Zhang
    •  & Jun Qin

  • Article
    | Open Access

    The Androgen Receptor (AR) is the main driver of prostate cancer and functions in conjunction with chromatin modifications. Here, the authors comprehensively profile 100 primary prostate carcinomas by sequencing RNA transcripts in combination with ChIP-sequencing for AR and the active histone marks H3K27ac, H3K4me3 and repressive mark H3K27me3.

    • Suzan Stelloo
    • , Ekaterina Nevedomskaya
    •  & Wilbert Zwart

  • Article
    | Open Access

    While young muscle faithfully regenerates damaged myofibers, aged muscle is impaired. Here the authors show the “anti-aging” protein α-Klotho is upregulated in young muscle after damage via promoter demethylation and this regulation is lost in aging, resulting in mitochondrial damage and an impaired healing response.

    • A. Sahu
    • , H. Mamiya
    •  & F. Ambrosio

  • 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

    The effects of epigenetic regulators on different tumor cell populations can affect their potential as anticancer targets. In this study, the authors demonstrate that the histone methyltransferase G9a is a suppressor of lung tumor-propagating cells and tumor progression, acting through chromatin modification with MMP10 as one of its targets for metastasis regulation.

    • S. P. Rowbotham
    • , F. Li
    •  & C. F. Kim

  • Article
    | Open Access

    The construction of complex RNA-delivered genetic circuits in mammalian cells is challenging, though offers advantages over DNA circuits in clinical use. Here the authors construct a set of logic gates that respond to multiple miRNAs and demonstrate an apoptosis-regulatory AND gate.

    • Satoshi Matsuura
    • , Hiroki Ono
    •  & Hirohide Saito

  • Article
    | Open Access

    Hippo-YAP pathway plays an important role in cancers; however the in vivo relevance of YAP/TAZ target genes is unclear. Here, the authors show that NUAK2 is a target of YAP and participates in a feedback loop to maximize YAP activity. Inhibition of NUAK2 suppresses YAP-driven hepatomegaly and liver cancer growth, offering a new target for cancer therapy.

    • Wei-Chien Yuan
    • , Brian Pepe-Mooney
    •  & Fernando D. Camargo

  • Article
    | Open Access

    DNA2 encodes a 5′ flap DNA endonuclease involved in replication and DNA double strand break processing. Here the authors by using a conditional degron system together with electron microscopy characterize the role played by Dna2 and Pif1 helicase during unperturbed DNA replication in S. cerevisiae.

    • Silvia Emma Rossi
    • , Marco Foiani
    •  & Michele Giannattasio

  • Article
    | Open Access

    Transient receptor potential vanilloid channel 3 (TRPV3) responds to temperature and sensitizes upon repeated stimulation with either heat or agonists. Here authors present the cryo-EM structures of apo and sensitized human TRPV3 and describe the structural basis of sensitization.

    • Lejla Zubcevic
    • , Mark A. Herzik Jr.
    •  & Seok-Yong Lee

  • Article
    | Open Access

    Chromothripsis and chromoanasynthesis lead to locally clustered rearrangements affecting one or a few chromosomes, but their impact on cancer development and progression is unclear. Here the authors analyse the role of DNA repair factors in brain tumors by whole-genome sequencing of tumors from mouse models of medulloblastoma or high grade gliomas.

    • Manasi Ratnaparkhe
    • , John K. L. Wong
    •  & Aurélie Ernst

  • Article
    | Open Access

    Staphylococcal pathogens adhere to their human targets using adhesins, which can withstand extremely high forces. Here, authors use single-molecule force spectroscopy to determine the similarly high unfolding forces of B domains that link the adhesin to the bacterium.

    • Lukas F. Milles
    • , Eduard M. Unterauer
    •  & Hermann E. Gaub

  • Article
    | Open Access

    REX1 has been shown to regulate pluripotency of ESCs, genomic imprinting and preimplantation development in mice. Here the authors provide evidence that REX1 is the prime target of RNF12 E3 ubiquitin ligase and that Rex1 removal rescues the Rnf12 knockout phenotype in imprinted X chromosome inactivation in mice.

    • Cristina Gontan
    • , Hegias Mira-Bontenbal
    •  & Joost Gribnau

  • Article
    | Open Access

    Transcription preinitiation complex assembly begins with the recognition of the gene promoter by the TATA-box Binding Protein-containing TFIID complex. Here the authors present a Cryo-EM structure of promoter-bound yeast TFIID complex, providing a detailed view of its subunit organization and promoter DNA contacts.

    • Olga Kolesnikova
    • , Adam Ben-Shem
    •  & Gabor Papai

  • Article
    | Open Access

    Chromodomain Helicase DNA-binding (CHD) proteins have been implicated in neurodevelopmental processes. Here, the authors identify missense variants in CHD3 that disturb its chromatin remodeling activities and cause a neurodevelopmental disorder with macrocephaly and speech and language impairment.

    • Lot Snijders Blok
    • , Justine Rousseau
    •  & Philippe M. Campeau

  • Article
    | Open Access

    The NuRD complex plays an important role in regulating lineage commitment and cell fate during early embryonic development. Here the authors present an integrative analysis of MBD3/NuRD composition and binding in mouse embryonic stem cells and neural progenitor cells, providing a molecular basis for genome-wide NuRD localization

    • Susan L. Kloet
    • , Ino D. Karemaker
    •  & Michiel Vermeulen

  • Article
    | Open Access

    Activation of PDGFRA by genomic aberrations contributes to tumor progression in several tumor types. Here, the authors perform functional characterization of 16 novel PDGFRA mutations identified from different tumor types and demonstrate that a neomorphic PDGFRA extracellular domain driver mutation is resistant to PDGFRA targeted therapies.

    • Carman K. M. Ip
    • , Patrick K. S. Ng
    •  & Gordon B. Mills

  • Article
    | Open Access

    The function of most lncRNA is unknown. Here, the authors show that transcriptional read-through at the Arabidopsis SVALKA locus produces a cryptic lncRNA that overlaps with the neighboring cold-responsive CBF1 gene and limits CBF1 expression via an RNA polymerase II collision-based mechanism.

    • Peter Kindgren
    • , Ryan Ard
    •  & Sebastian Marquardt

  • Article
    | Open Access

    Biomimetic “noses” have been proposed to replace trained animals for chemical detection. Here the authors select 31 mouse olfactory receptors (ORs), based on a large cell-based screen of >800 ORs against seven chemicals, to build an OR-based sensor able to discriminate structurally similar compounds.

    • Hitoshi Kida
    • , Yosuke Fukutani
    •  & Hiroaki Matsunami

  • Article
    | Open Access

    Vascular smooth muscle cell (VSMC) accumulation is associated with cardiovascular disease. Here, the authors combine single-cell RNA sequencing with lineage labelling to profile VSMC heterogeneity in healthy mice. They show that upregulation of Sca1 in a rare VSMC subpopulation marks a cell phenotype that is prevalent in disease.

    • Lina Dobnikar
    • , Annabel L. Taylor
    •  & Helle F. Jørgensen

  • Article
    | Open Access

    The chaperone Hsp90 plays a key role in maintaining cellular homeostasis. Here the authors provide structural insights into substrate recognition and the pro-folding mechanism of Hsp90/co-chaperone complexes by studying the complex of Hsp90 with its co-chaperone FKBP51 and the substrate Tau bound Hsp90/FKBP51 ternary complex using a NMR based integrative approach.

    • Javier Oroz
    • , Bliss J. Chang
    •  & Markus Zweckstetter

  • Article
    | Open Access

    DNA methylation and H3K9 dimethylation are two linked epigenetic marks of silenced chromatin in plants that depend on the activity of CMT3/2 and SUVH4/5/6. Here the authors identify AGDP1 as an H3K9me2-binding protein required for heterochromatic non-CG DNA methylation, H3K9 dimethylation, and transcriptional silencing.

    • Cuijun Zhang
    • , Xuan Du
    •  & Jian-Kang Zhu

  • Article
    | Open Access

    The role of protein arginine methyltransferases (PRMTs) in epigenetic regulation in cancer is still poorly understood. Here, the authors show that PRMT2 is highly expressed in Glioblastoma multiforme (GBM) and provide evidence that PRMT2 acts as a transcriptional co-activator for oncogenic gene expression programs, at least partly dependent on its H3R8me2a activity, in GBM pathogenesis.

    • Feng Dong
    • , Qian Li
    •  & Xudong Wu

  • Article
    | Open Access

    AUXIN RESPONSE FACTORS (ARFs) are a family of plant-specific transcriptional factors involved in auxin signaling. Here, the authors adapt DAP-seq technology to show the binding landscape of 14 maize ARFs and reveal class-specific binding properties and transcriptional coordination by ARFs from different classes.

    • Mary Galli
    • , Arjun Khakhar
    •  & Andrea Gallavotti

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