Molecular biology articles within Nature Communications

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  • Article
    | Open Access

    Endothelial cells (ECs) are promising strategies to treat vasculopathies but little is known about the factors that sustain EC identity and govern functional integration into vasculature after transplantation. Here the authors show that Ets factors and Sox17 convert nonvascular cells to vascular cells with stable EC identity and function.

    • William Schachterle
    • , Chaitanya R. Badwe
    •  & Shahin Rafii
  • Article
    | Open Access

    DNA sliding clamps are ring-shaped proteins that encircle DNA and harbour polymerases and other factors that promote processive DNA replication. Here the authors use X-ray crystallography, NMR and MD simulations to propose a model for a PCNA sliding mechanism that relies on short-lived polar interactions.

    • Matteo De March
    • , Nekane Merino
    •  & Alfredo De Biasio
  • Article
    | Open Access

    Riboswitches are non-coding RNA elements that detect metabolites and control expression by regulating mRNA levels or translation. Here, the authors provide evidence that theE. coli thiC riboswitch has a pause site in the translation initiation region that acts as a checkpoint for thiCexpression.

    • Adrien Chauvier
    • , Frédéric Picard-Jean
    •  & Daniel A. Lafontaine
  • Article
    | Open Access

    In skeletal muscle progenitors, EZH2 maintains myogenic genes in a repressed state, but during differentiation its levels are reduced via unknown mechanisms. Here the authors show that during myogenesis, p38α kinase phosphorylates EZH2 and targets it for degradation by the ubiquitin ligase PRAJA1.

    • Silvia Consalvi
    • , Arianna Brancaccio
    •  & Daniela Palacios
  • Article
    | Open Access

    The cohesin complex maintains genome integrity by ensuring correct sister-chromatid segregation during mitosis and meiosis. Here, Chaoet al. present a pseudo-atomic model of the full-length Scc2–Scc4 cohesin loader complex and reveal key Scc2 surfaces crucial for cohesin loading.

    • William C. H. Chao
    • , Yasuto Murayama
    •  & Martin R. Singleton
  • Article
    | Open Access

    The protein tyrosine kinase c-Src is a renowned proto-oncogene with pleiotropic effects. Here, the authors show that c-Src induces the metabolic reprogramming of cancer cells by phosphorylating hexokinases HK1 and HK2, which in turns lead to increased HK catalytic activity and consequent enhancement of glycolysis.

    • Jia Zhang
    • , Suili Wang
    •  & Qinxi Li
  • Article
    | Open Access

    Cell–cell adhesion and oriented cell division play key roles in tissue architecture, but how they are coordinated is not known. Here, the authors show that E-cadherin interacts with LGN, and thereby provides a cortical cue that serves to stabilize cortical attachment of astral microtubules at cell–cell adhesions, thus orienting the mitotic spindle.

    • Martijn Gloerich
    • , Julie M. Bianchini
    •  & W. James Nelson
  • Article
    | Open Access

    Nonsense-mediated mRNA decay (NMD) is a quality control pathway that recognizes and degrades transcripts harbouring nonsense mutations. Here the authors show that the ATPase activity of UPF1 mediates functional interactions between the NMD machinery and ribosomes required for efficient ribosome release at premature termination codons.

    • Lucas D. Serdar
    • , DaJuan L. Whiteside
    •  & Kristian E. Baker
  • Article
    | Open Access

    mRNA surveillance is essential to maintain homeostasis in eukaryotes and is activated by mRNAs lacking a stop codon. Here the authors describe a high resolution cryo-EM structure of a nonstop complex that shows how arrested ribosome recognition is achieved during Dom34-mediated mRNA surveillance.

    • Tarek Hilal
    • , Hiroshi Yamamoto
    •  & Christian M.T. Spahn
  • Article
    | Open Access

    Many chromatin modifying proteins, including BRDT, contain bromodomains, which are known to interact with nucleosomes. Here, the authors find that BRDT interacts with nucleosomes via only one of its two bromodomains, and that the interaction involves contacts with DNA as well as acetylated histones.

    • Thomas C. R. Miller
    • , Bernd Simon
    •  & Christoph W. Müller
  • Article
    | Open Access

    Bacteria may respond to a change in environment by using alternative transcriptional start sites. Here, the authors use a novel genome-wide capture and reverse transcription method to find substrate-specific start sites for hundreds of genes at single base resolution inClostridium phytofermentans.

    • Magali Boutard
    • , Laurence Ettwiller
    •  & Andrew C. Tolonen
  • Article
    | Open Access

    DNA damage arising from replication stress is well studied, but the effect of mitotic errors on genome integrity is less understood. Here the authors knock down 47 mitotic regulators and record how they impact on DNA breakage events, providing a resource for future studies on the relation between cell division and genome integrity.

    • Ronni S. Pedersen
    • , Gopal Karemore
    •  & Claudia Lukas
  • Article
    | Open Access

    The RNA binding protein TRBP is a component of the Dicer complex but its role in microRNA biogenesis remains poorly understood. Here the authors use a crowded RNA environment and single-molecule imaging to show that TRBP acts as a gatekeeper to prevent Dicer engagement with pre miRNA-like substrates.

    • Mohamed Fareh
    • , Kyu-Hyeon Yeom
    •  & Chirlmin Joo
  • Article
    | Open Access

    In Drosophila ovarian follicle cells, piRNAs generated from RNA precursors are processed in cytoplasmic Yb-bodies. The authors identify the exportin and the exon junction complexes as required to transfer precursors to cytoplasm. They also show that Yb-body formation requires piRNA precursor export.

    • Cynthia Dennis
    • , Emilie Brasset
    •  & Chantal Vaury
  • Article
    | Open Access

    Transcriptional bursting is a potential source of cell-to-cell variability but the molecular mechanisms are unclear. Here the authors use single molecule imaging to analyse the kinetics of bursting on DNA and observe that bursting is an intrinsic property of RNA polymerases on DNA.

    • Keisuke Fujita
    • , Mitsuhiro Iwaki
    •  & Toshio Yanagida
  • Article
    | Open Access

    Werner Syndrome is an accelerated aging disorder marked by genome instability, large deletions and telomere fusions, hallmarks of aberrant DNA repair. Here the authors report a role for the WRN helicase in regulating the choice between classical and alternative non-homologous end-joning.

    • Raghavendra A. Shamanna
    • , Huiming Lu
    •  & Vilhelm A. Bohr
  • Article
    | Open Access

    Self-renewal of cancer stem cells can contribute to glioma progression. Here, the authors show that Notch1 activation in glioma stem cells induces expression of the lncRNATUG1, which promotes self-renewal through the repression of differentiation genes, and that targeting TUG1 represses glioma growth in vivo.

    • Keisuke Katsushima
    • , Atsushi Natsume
    •  & Yutaka Kondo
  • Article
    | Open Access

    Degradation of messenger RNA is a key regulatory step in controlling eukaryotic gene expression. Here the authors present xrFrag, a molecular tool to interrogate the extent and directionality of mRNA turnover by the detection of stabilized decay intermediates produced by several common decay pathways.

    • Volker Boehm
    • , Jennifer V. Gerbracht
    •  & Niels H. Gehring
  • Article
    | Open Access

    The correct folding of proteins often requires the intervention molecular chaperones, which can occur co-translationally. Here the authors identify elements of yeast Ssb (Hsp70) that mediate ribosomal binding, and suggest a mechanism that directs efficient interaction of Ssb with the nascent chain.

    • Marie A. Hanebuth
    • , Roman Kityk
    •  & Elke Deuerling
  • Article
    | Open Access

    RBM7 and ZCCHC8 are two core subunits of the Nuclear Exosome Targeting complex, which regulates the degradation of selected non-coding RNAs in human cells. Here, the authors use structural and biochemical methods to show how ZCCHC8 recruits RBM7 in the complex, leaving the RNA binding site accessible and revealing possible implications for splicing.

    • Sebastian Falk
    • , Ksenia Finogenova
    •  & Elena Conti
  • Article
    | Open Access

    H3K36 methylation by Set2 targets Rpd3S histone deacetylase to transcribed mRNA genes, repressing internal cryptic promoters and modulating elongation. Here, the authors provide evidence that the Set2-Rpd3S pathway also regulates dynamic expression of mRNAs and lncRNAs.

    • Ji Hyun Kim
    • , Bo Bae Lee
    •  & TaeSoo Kim
  • Article
    | Open Access

    Maintenance of chromatin structure in coding regions is partially dependent on transcription, with histone methyltransferase Set2 playing a role in this process. Here, the authors provide evidence that Set2 regulates repression of a specific set of antisense RNAs embedded within the coding genes.

    • Swaminathan Venkatesh
    • , Hua Li
    •  & Jerry L. Workman
  • Article
    | Open Access

    Renal tumour-initiating cells (T-ICs) contribute to tumour initiation and progression. Here, the authors show that lncARSR regulates TICs by blocking LATS1-induced YAP phosphorylation facilitating YAP nuclear translocation, which promotes lncARSR transcription, thus forming a feed-forward circuit to promote TIC expansion.

    • Le Qu
    • , Zhenjie Wu
    •  & Linhui Wang
  • Article
    | Open Access

    Genome wide association studies have identified multiple risk loci for multiple myeloma. Here, the authors show that the expression of CDCA7Lis associated with patient survival and expression of the gene is influenced by a risk variant at 7p15.3, which creates a transcription factor binding site for IRF4.

    • Ni Li
    • , David C. Johnson
    •  & Richard S. Houlston
  • Article
    | Open Access

    Robo4 is a transmembrane protein that regulates vascular permeability. Zhang et al. now reveal the mechanism of Robo4 action and show that Robo4 and UncB are required for VEGF-mediated regulation of vascular barrier by suppressing VEGF-induced phosphorylation of its receptor Vegfr2 on Y949.

    • Feng Zhang
    • , Claudia Prahst
    •  & Anne Eichmann
  • Article
    | Open Access

    How archaeal viruses perturb host transcription machinery is poorly understood. Here, the authors provide evidence that the archaeo-viral transcription factor ORF145/RIP targets host RNA polymerase, repressing its activity.

    • Carol Sheppard
    • , Fabian Blombach
    •  & Finn Werner
  • Article
    | Open Access

    GCN5 inhibits hepatic gluconeogenesis through acetylation of PGC-1α. Here the authors show that GCN5 also activates hepatic gluconeogenesis by acetylating histone H3K9, and that the affinity of GCN5 for its different substrates is regulated via phosphorylation at S275 by PKA in a CITED2-dependent manner.

    • Mashito Sakai
    • , Tomoko Tujimura-Hayakawa
    •  & Michihiro Matsumoto
  • Article
    | Open Access

    Epithelial-to-mesenchymal transition is a key process in tumorigenesis but little is known about the molecular mechanism regulating such process at the translational level. Here, the authors identify a subset of mRNAs important for this process that are specifically modulated by the RNA-binding protein CELF1.

    • Arindam Chaudhury
    • , Shebna Cheema
    •  & Joel R. Neilson
  • Article
    | Open Access

    BRCA1 loss can result in collapse of replication forks into DNA double strand breaks that can contribute to malignant transformation. Here, the authors find that BRCA1 promotes the expression of RRM2 protecting glioblastoma cells from replication stress, DNA damage and apoptosis.

    • Rikke D. Rasmussen
    • , Madhavsai K. Gajjar
    •  & Petra Hamerlik
  • Article
    | Open Access

    Heteroplasmy, in which mutant and wild-type mitochondrial DNA (mtDNA) coexist in a cell, can result in diseases. Here the authors generate transgenic flies with heteroplasmic mtDNA in flight muscles, and show that stimulation of autophagy, or a decrease in mitofusin, promotes clearance of mutant mtDNA.

    • Nikolay P. Kandul
    • , Ting Zhang
    •  & Ming Guo
  • Article
    | Open Access

    Centromeres are centrochromatin domains with CENP-A and H3 nucleosomes carrying transcription-associated modifications. Here the authors target synthetic modules to the centromeres to show that transcription plus histone modifications are required for CENP-A assembly and centrochromatin maintenance.

    • Oscar Molina
    • , Giulia Vargiu
    •  & William C. Earnshaw
  • Article
    | Open Access

    KDM4 histone demethylases target specific chromatin regions by a mechanism that is not fully characterised. Here, the authors identify trimethyl-lysine histone-binding preferences for closely related KDM4 double tudor domains and use structural and biochemical information to examine the molecular details of this interaction.

    • Zhangli Su
    • , Fengbin Wang
    •  & John M. Denu
  • Article
    | Open Access

    Mycobacteria can adapt to the stress of human infection by entering a dormant state. Here the authors show that hypoxia-induced dormancy in M. bovisBCG involves the reprogramming of tRNA wobble modifications and copy numbers, coupled with biased use of synonymous codons in survival genes.

    • Yok Hian Chionh
    • , Megan McBee
    •  & Peter C. Dedon
  • Article
    | Open Access

    The expansion of trinucleotide repeats has been linked to several neurodegenerative disorders. Here, the authors show that the CRISPR-Cas9 nuclease induces both expansions and contractions of the repeat region, whereas the nickase leads predominantly to contractions.

    • Cinzia Cinesi
    • , Lorène Aeschbach
    •  & Vincent Dion
  • Article
    | Open Access

    Some bacterial toxin-antitoxin systems consist of a labile antitoxin that inhibits a toxin, and a chaperone that stabilizes the antitoxin. Here, Bordes et al. identify a sequence within the antitoxin to which the chaperone binds and which can be transferred to other proteins to make them chaperone-dependent.

    • Patricia Bordes
    • , Ambre Julie Sala
    •  & Pierre Genevaux
  • Article
    | Open Access

    The chromatin-associated protein AKAP95 is known for its chromatin-related functions including enhancing transcription. Here the authors show that AKAP95 interacts with the splicing regulatory factors as well as RNAs to regulate the inclusion of exons and pre-mRNA splicing.

    • Jing Hu
    • , Alireza Khodadadi-Jamayran
    •  & Hao Jiang