Molecular biology articles within Nature Communications

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  • Article
    | Open Access

    Circadian clock regulates hepatic gene expression and functions. Here Chao et al. show that alteration of circadian clock genes by Period deletion induces polyploidy in hepatocytes due to impaired regulation of Erk signaling by mitogen-activated protein kinase phosphatase 1.

    • Hsu-Wen Chao
    • , Masao Doi
    •  & Hitoshi Okamura

  • Article
    | Open Access

    The histone chaperone nucleoplasmin (Npm) stores histones H2A/H2B in the egg and embryo. Here, the authors use NMR to show that Npm’s intrinsically disordered tail domain controls histone binding at an acidic stretch, which is autoregulated through direct competition with its basic C-terminus.

    • Christopher Warren
    • , Tsutomu Matsui
    •  & David Shechter

  • Article
    | Open Access

    The dopamine transporter (DAT), a regulator of dopamine homeostasis in the brain, and sigma-1 receptor (σ1R), an endoplasmic reticulum membrane protein, are both implicated in drug addiction. In this work, the authors investigate how σ1R modulates DAT response to methamphetamine.

    • Danielle O. Sambo
    • , Min Lin
    •  & Habibeh Khoshbouei

  • Article
    | Open Access

    MICAL Redox enzymes post-translationally modify F-actin to promote its cellular destabilization. Here, the authors present a 3.9Å cryoEM structure of Mical-oxidized F-actin, showing its nucleotide-state dependent dynamic instability and susceptibility to cofilin-induced severing in the presence of inorganic phosphate.

    • Elena E. Grintsevich
    • , Peng Ge
    •  & Emil Reisler

  • Article
    | Open Access

    The yeast and human RNA exosome is structurally related to prokaryotic phosphorylases but degrades RNA only via associated hydrolytic activities. Here the authors show that the RNA exosome of plants, and likely those of a few basal eukaryotes, combines phosphorolytic and hydrolytic activities to degrade RNA.

    • Natalia Sikorska
    • , Hélène Zuber
    •  & Dominique Gagliardi

  • Article
    | Open Access

    Phosphoinositides are enriched in the nucleus and accumulate upon DNA damage but their role in responding to DNA damage is poorly defined. Here, the authors show that phosphoinositides rapidly accumulate at DNA damage sites and are required for ATR recruitment and subsequent Chk1 activation.

    • Yu-Hsiu Wang
    • , Anushya Hariharan
    •  & Michael P. Sheetz

  • Article
    | Open Access

    The oncogenic activity of EBNA1 protein is unknown; it contains a glycine and alanine repeat sequence (GAr) which regulates its own translation in cis. Here the authors show that GAr stimulates PI3Kδ-mediated induction of E2F1 translation, leading to c-Myc induction and stimulation of proliferation.

    • Sivakumar Vadivel Gnanasundram
    • , Slovénie Pyndiah
    •  & Robin Fåhraeus

  • Article
    | Open Access

    Spleen protein tyrosine kinase (Syk) has so far been mainly studied in haematopoietic and immune cells. Here, the authors show that Syk also has a role in brown adipose tissue, where it regulates the formation of brown adipocytes and their thermogenic activation in response to β-adrenergic stimulation.

    • Marko Knoll
    • , Sally Winther
    •  & Harvey F. Lodish

  • Article
    | Open Access

    Several families of natural compounds target core components of the pre-mRNA splicing machinery and display anti-tumor activity. Here the authors show that particular sequence features can be linked to drug response, and that drugs with very similar chemical structures display substantially different effects on splicing regulation.

    • Luisa Vigevani
    • , André Gohr
    •  & Juan Valcárcel

  • Article
    | Open Access

    TERRA RNA is involved in maintaining stability during telomere repeat replication. Here the authors, by using CRISPR/Cas9, mutate CTCF-binding sites at start site of TERRA transcripts and find that subtelomeric CTCF facilitates telomeric DNA replication by promoting TERRA transcription.

    • Kate Beishline
    • , Olga Vladimirova
    •  & Paul M. Lieberman

  • Article
    | Open Access

    The activation of TGF-β signaling has been implicated in cancer metastasis. Here, the authors show that OTUD1 suppresses metastasis by antagonizing the TGF-β pathway via the deubiquitination of SMAD7, and its loss correlates with poor prognosis in breast cancer.

    • Zhengkui Zhang
    • , Yao Fan
    •  & Long Zhang

  • Article
    | Open Access

    SETDB1 is a histone methyltransferase that generates H3K9me3 marks in euchromatic regions. Here the authors show that the triple Tudor domain (3TD) of SETDB1 binds histone H3 tails containing K14 acetylation combined with K9 methylation, and that the K9me–K14ac modification defines a novel chromatin state enriched at SETDB1 binding sites.

    • Renata Z. Jurkowska
    • , Su Qin
    •  & Albert Jeltsch

  • Article
    | Open Access

    Smad transcription factors are part of the TGF-β signal transduction pathways and are recruited to the genome by cell lineage-defining factors. Here, the authors identify specific Smad binding GC-rich motifs and provide structural information showing Smad3 and Smad4 bound to these motifs.

    • Pau Martin-Malpartida
    • , Marta Batet
    •  & Maria J. Macias

  • Article
    | Open Access

    Protein ADP-ribosylation has emerged as a key post translational modification that regulates several stress responses. Here the authors characterize ARH3 as a major serine-specific mono–ADP-­ribosylhydrolase and use a proteomics approach to identify the cellular targets of ARH3.

    • Jeannette Abplanalp
    • , Mario Leutert
    •  & Michael O. Hottiger

  • Article
    | Open Access

    Precise orchestration of gene expression regulation upon DNA damage is essential for genome integrity. Here the authors identify a novel widespread stress-triggered defence mechanism that promotes rapid transcription-driven genomic surveillance thus limiting mutagenesis and shaping cancer genomes.

    • Matthieu D. Lavigne
    • , Dimitris Konstantopoulos
    •  & Maria Fousteri

  • Article
    | Open Access

    The double-strand breaks generated by CRISPR-Cas systems are the target of multiple DNA repair pathways. Here the authors find incompatibility between NHEJ and type II-A CRISPR-Cas systems due to Csn2 mediated inhibition of end-joining.

    • Aude Bernheim
    • , Alicia Calvo-Villamañán
    •  & David Bikard

  • Article
    | Open Access

    Porins, like OmpG, are embedded in the outer membrane of bacteria and facilitate uptake and secretion of nutrients and ions. Here the authors present a protocol for solid state NMR structure determination of proteins larger than 25 kDa and use it to structurally characterize membrane embedded OmpG.

    • Joren S. Retel
    • , Andrew J. Nieuwkoop
    •  & Hartmut Oschkinat

  • Article
    | Open Access

    Mutations in VHL have been linked to clear cell renal cancer, but the molecular mechanisms involved remain unclear. Here the authors generate a mouse model closely mimicking the human disease and show that VHL loss induces DNA replication stress that is rescued by the concomitant loss of PBRM1 permitting transformation.

    • Judit Espana-Agusti
    • , Anne Warren
    •  & Athena Matakidou

  • Article
    | Open Access

    Excessive inflammation can be tissue destructive and contributes to auotinflammatory diseases and sepsis pathology. Here the authors show that the lncRNA Mirt2 is an endogenous negative feedback regulator of LPS-induced inflammation by limiting ubiquitination of TRAF6 and NF-κB activation.

    • Meng Du
    • , Lin Yuan
    •  & Kai Huang

  • Article
    | Open Access

    Traditionally marker-based approaches are used to define haematopoietic cell type or state. Here, the authors use single-cell RNA-seq to establish a cellular hierarchy of lineage development in zebrafish haematopoiesis, and propose a refined model of developmental progression of haematopoietic cells.

    • Emmanouil I. Athanasiadis
    • , Jan G. Botthof
    •  & Ana Cvejic

  • Article
    | Open Access

    A nucleotide repeat expansion in C9orf72 is a common genetic cause of neurodegenerative disorders. Here, the authors provide insight into the molecular mechanism by which this repeat undergoes Repeat-Associated Non-AUG (RAN) translation, implicating the integrated stress response and eIF2α phosphorylation.

    • Katelyn M. Green
    • , M. Rebecca Glineburg
    •  & Peter K. Todd

  • Article
    | Open Access

    The bacterial chaperone Trigger Factor (TF) is a dynamic protein and its dimer structure is unknown. Here the authors present a protocol combining NMR, computational and biophysical methods for the structural characterization of large dynamic protein complexes and show that TF forms a symmetric head-to-tail dimer.

    • Leonor Morgado
    • , Björn M. Burmann
    •  & Sebastian Hiller

  • Article
    | Open Access

    RNA-cleaving DNA enzymes are catalytic DNA that can cleave RNA in a sequence-specific manner. Here, the authors report three crystal structures of the 8–17 DNAzyme that include the pre-catalytic state of the RNA cleavage reaction, providing insight into the catalytic mechanism and may guide the rational design of DNAzymes.

    • Hehua Liu
    • , Xiang Yu
    •  & Jianhua Gan

  • Article
    | Open Access

    Polη is a key player in translesion DNA synthesis. Here, the authors uncover that, in response to DNA damage, Polη undergoes O-GlcNAcylation at threonine 457 by O-GlcNAc transferase to facilitate the timely disassembly of Polη after DNA lesion bypass.

    • Xiaolu Ma
    • , Hongmei Liu
    •  & Caixia Guo

  • Article
    | Open Access

    The treatment of multiple myeloma is challenging due to high relapse rates. Here the authors show that expression of ADAR1 correlates with poor patient outcomes, and that ADAR1-mediated editing of GLI1 is a mechanism relevant in the context of multiple myeloma progression and drug resistance.

    • Elisa Lazzari
    • , Phoebe K. Mondala
    •  & Catriona H. M. Jamieson

  • Article
    | Open Access

    Transcript cleavage factors such as eukaryotic TFIIS assist the resumption of transcription following RNA pol II backtracking. Here the authors find that one of the Sulfolobus solfataricus TFIIS homolog—TFS4—has evolved into a potent RNA polymerase inhibitor potentially involved in antiviral defense.

    • Thomas Fouqueau
    • , Fabian Blombach
    •  & Finn Werner

  • Article
    | Open Access

    Little is known about the changes in mRNA splicing, processing and stability that can alter gene expression during heart failure. Here, the authors show that BEX1 is induced during heart failure and is part of a ribonucleoprotein complex enhancing the expression and stability of proinflammatory genes.

    • Federica Accornero
    • , Tobias G. Schips
    •  & Jeffery D. Molkentin

  • Article
    | Open Access

    Post-translational modification has a variety of regulatory functions for important immune molecules. Here the authors use B-cell specific knockout mice to show how O-GlcNAcylation is required for functional B cell responses and humoral immunity.

    • Jung-Lin Wu
    • , Ming-Feng Chiang
    •  & Kuo-I Lin

  • Article
    | Open Access

    Centromeres and large-scale structural variants evolve and contribute to genome diversity during vertebrate speciation. Here Ichikawa et al perform de novo long-read genome assembly of three inbred medaka strains, and report long-range structure of centromeres and their methylation as well as correlation of structural variants with differential gene expression.

    • Kazuki Ichikawa
    • , Shingo Tomioka
    •  & Shinich Morishita

  • Article
    | Open Access

    Changes in chromatin structure have been linked to organismal ageing. Here the authors show that altered histone expression and mitochondrial stress during C. elegans development result in chromatin changes and a cytosolic stress response that affects organismal longevity, and depends on HSF-1 and the chromatin remodeller, ISW-1.

    • Olli Matilainen
    • , Maroun S. Bou Sleiman
    •  & Johan Auwerx

  • Article
    | Open Access

    Break-induced replication (BIR) is a double-strand break repair pathway that can lead to genomic instability. Here the authors show that the absence of Srs2 helicase during BIR leads to uncontrolled binding of Rad51 to single-stranded DNA, which promotes the formation of toxic intermediates that need to be resolved by Mus81 or Yen1.

    • Rajula Elango
    • , Ziwei Sheng
    •  & Anna Malkova

  • Article
    | Open Access

    Excision of internal transcribed spacer 2 (ITS2) within eukaryotic pre-ribosomal RNA is essential for ribosome function. Here, the authors reconstitute the entire cycle of ITS2 processing in vitro using purified components, providing insights into the cleavage process and demonstrating that 26S pre-rRNA processing necessarily precedes 7S pre-rRNA processing.

    • Lisa Fromm
    • , Sebastian Falk
    •  & Ed Hurt

  • Article
    | Open Access

    Using genome-wide miRNA mimic and hairpin inhibitor screens, Li et al. identify 31 miRNAs that either inhibit or promote hepatitis C virus (HCV) replication at different steps of the viral life cycle. Furthermore, human liver biopsies show that HCV down-regulates identified miRNAs with antiviral function.

    • Qisheng Li
    • , Brianna Lowey
    •  & T. Jake Liang

  • Article
    | Open Access

    SUMO and ubiquitin are key signal transducers in several cellular processes including the DNA-damage response. Here the authors describe a method for selective enrichment of ubiquitin substrates for E3 ligases from complex cellular proteomes and identify the SUMO conjugation machinery as direct RNF4 substrates.

    • Ramesh Kumar
    • , Román González-Prieto
    •  & Alfred C. O. Vertegaal

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