Molecular biology articles within Nature Communications

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  • Article
    | Open Access

    Mutations in mitochondrially-encoded tRNA genes can lead to mitochondrial disorders. Here the authors use next generation RNA sequencing to reveal the role of a N1 -methyladenosine modification in tRNALys MERR patients for translation elongation and the stability of selected nascent chains.

    • Uwe Richter
    • , Molly E. Evans
    •  & Brendan J. Battersby
  • Article
    | Open Access

    Otefin is a nuclear lamina protein required for survival of Drosophila germ stem cells. Here the authors show that nuclear lamina dysfunction resulting from loss of Otefin activates a DNA damage-independent germ stem cell-specific checkpoint, mediated by the ATR and Chk2 kinases, which ensures that healthy gametes are passed on to the next generation.

    • Lacy J. Barton
    • , Tingting Duan
    •  & Pamela K. Geyer
  • Article
    | Open Access

    Exosomes mediate cell-to-cell communication by transporting proteins, mRNAs, and miRNAs but the mechanisms of protein sorting to exosomes are poorly understood. Here, the authors uncover that ubiquitin-like 3 (UBL3) regulates protein sorting to exosomes by acting as a posttranslational modification.

    • Hiroshi Ageta
    • , Natsumi Ageta-Ishihara
    •  & Kunihiro Tsuchida
  • Article
    | Open Access

    Cells with damaged DNA can permanently exit the cell cycle during the G2 phase or recover spontaneously entering mitosis. Here the authors reveal that the decision to exit from the cell cycle in G2 is dependent on the presence of repair intermediates associated with homologous recombination.

    • F. M. Feringa
    • , J. A. Raaijmakers
    •  & R. H. Medema
  • Article
    | Open Access

    How repair pathway selection occurs is still a matter of debate and many factors have been associated to this function. Here the authors provide insight into the role of FAM35A and C20ORF196, two REV7-interacting proteins, which are recruited at double-strand breaks to promote non-homologous end joining repair.

    • Shengxian Gao
    • , Sumin Feng
    •  & Dongyi Xu
  • Article
    | Open Access

    Loss of Fancd2 leads to replication stress intolerance and Fanconi Anemia, where haematopoietic stem cell (HSC) function is compromised. Here, the authors show that Lnk/Sh2b3 loss restores HSC proliferation and survival in Fancd2 knockout mice and ameliorates replication stress in a cytokine/JAK2 signaling dependent manner.

    • Joanna Balcerek
    • , Jing Jiang
    •  & Wei Tong
  • Article
    | Open Access

    TNF mediated inflammation is critical in autoimmune mediated pathology, however many patients are refractory to current anti-TNF therapeutics. Here the authors show induction of several death ligands, in addition to TNF is sufficient to cause fatal dermatitis in a LUBAC deficient murine model of disease.

    • Lucia Taraborrelli
    • , Nieves Peltzer
    •  & Henning Walczak
  • Article
    | Open Access

    Loss of Polycomb repressive complex 1 (PRC1) proteins usually results in both chromatin unfolding and ectopic transcription. Here, the authors analyze the temporal function of two PRC1 proteins during Drosophila embryogenesis and provide evidence that PRC1 maintains gene silencing by folding chromatin domains.

    • Thierry Cheutin
    •  & Giacomo Cavalli
  • Article
    | Open Access

    While a majority of histones are replaced by protamines during spermatogenesis, a small amount is retained in mammalian spermatozoa. Here the authors develop a method to purify histones from replacement-completed sperm (HRCS), completely solubilize histones from cross-linked HRCS without MNase digestion, and map histone-binding sites in these cells.

    • Keisuke Yoshida
    • , Masafumi Muratani
    •  & Shunsuke Ishii
  • Article
    | Open Access

    Targeting the glycolytic PFKFB3 enzyme is being studied as a therapeutic strategy against cancer. Here the authors identify PFKFB3 as being involved in homologous recombination (HR) repair of DNA double strand breaks (DSBs) and present a PFKFB3 inhibitor.

    • Nina M. S. Gustafsson
    • , Katarina Färnegårdh
    •  & Thomas Helleday
  • Article
    | Open Access

    Upon ligand binding epidermal growth factor receptor (EGFR) dimerizes and activates its intrinsic kinase to auto-phosphorylate EGFR. Here, the authors engineer and image a FRET-based conformational EGFR indicator which reveals that activation loop phosphorylation induces a catalytically active conformation in EGFR monomers.

    • Martin Baumdick
    • , Márton Gelléri
    •  & Philippe I. H. Bastiaens
  • Article
    | Open Access

    Self-interacting chromatin domains encompass genes and their cis-regulatory elements. Here the authors use high-resolution chromosome conformation capture and super-resolution imaging to study a 70 kb domain that includes the mouse α-globin regulatory locus and find that a tissue-specific self-interacting chromatin domain forms independently of enhancer-promoter interactions.

    • Jill M. Brown
    • , Nigel A. Roberts
    •  & Veronica J. Buckle
  • Article
    | Open Access

    Single-cell DNA methylome profiling allows the study of epigenomic heterogeneity in tissues but has been impeded by library quality. Here the authors demonstrate snmC-seq2 which improves mapping, throughput and library complexity.

    • Chongyuan Luo
    • , Angeline Rivkin
    •  & Joseph R. Ecker
  • Article
    | Open Access

    Although Ftx lncRNA has been linked to X-chromosome inactivation, its physiological roles in vivo remain unclear. Here the authors show that deletion of mouse Ftx causes eye abnormalities similar to human microphthalmia in a subset of female mice but rarely in males and provide evidence that Ftx plays a role in gene silencing on the inactive X chromosome.

    • Yusuke Hosoi
    • , Miki Soma
    •  & Shin Kobayashi
  • Article
    | Open Access

    Roquin targets are known to contain two types of sequence-structure motifs, the constitutive and the alternative decay elements (CDE and ADE). Here, the authors describe a linear Roquin binding element (LBE) also involved in target recognition, and show that Roquin binding affects the translation of a subset of targeted mRNAs.

    • Katharina Essig
    • , Nina Kronbeck
    •  & Vigo Heissmeyer
  • Article
    | Open Access

    Histones are recognized by epigenetic readers, which play essential roles in regulation of chromatin and transcription. Here the authors provide evidence that the ZZ-type zinc finger domain of ZZZ3 functions as a reader of histone H3, which is required for the ATAC complex-mediated maintenance of histone acetylation and gene activation.

    • Wenyi Mi
    • , Yi Zhang
    •  & Xiaobing Shi
  • Article
    | Open Access

    Neutrophilic granulocytes release their own DNA (NETosis) as neutrophil extracellular traps to capture pathogens. Here, the authors use time-resolved fluorescence and atomic force microscopy and reveal that NETosis is highly organized into three distinct phases with a clear point of no return defined by chromatin status.

    • Elsa Neubert
    • , Daniel Meyer
    •  & Sebastian Kruss
  • Article
    | Open Access

    Cell cycle and replication need to be tightly regulated to ensure genome stability in mammalian cells. Here the authors provide a link between chromatin structure and DNA replication regulation by showing that chromatin compaction limits replication licensing thereby promoting genome integrity.

    • Muhammad Shoaib
    • , David Walter
    •  & Claus S. Sørensen
  • Article
    | Open Access

    Impairment of DNA repair has been associated with neurodegeneration. Here the authors investigate the mechanisms of defects in repair caused by mutations in the RNA/DNA binding protein FUS in amyotrophic lateral sclerosis and elucidate its role in the DNA ligation during DNA single-strand break repair of oxidative breaks.

    • Haibo Wang
    • , Wenting Guo
    •  & Muralidhar L. Hegde
  • Article
    | Open Access

    Hofvander and colleagues compare the patterns of clonal evolution in different pathogenetic subgroups of sarcoma. They show that sarcomas driven by gene fusion or amplification display few additional changes over time, whereas sarcomas with complex karyotypes show a gradual increase of nucleotide- and chromosome-level mutations.

    • Jakob Hofvander
    • , Björn Viklund
    •  & Fredrik Mertens
  • Article
    | Open Access

    Fibro-adipogenic progenitors (FAPs) resident in skeletal muscle are involved in both regeneration and maladaptive processes. Here, the authors identify subpopulations of FAPs with biological activities implicated in physiological muscle repair that are altered in pathological conditions such as muscular dystrophies.

    • Barbora Malecova
    • , Sole Gatto
    •  & Pier Lorenzo Puri
  • Article
    | Open Access

    The RNA-induced silencing complex (RISC) represses gene expression via micro-RNA guided mRNA silencing. Here, the authors show that RISC component Argonaute 2 in the liver regulates energy metabolism by inducing microRNAs that cause metabolic disruption and by suppressing protein translation linked to AMPK activation.

    • Cai Zhang
    • , Joonbae Seo
    •  & Takahisa Nakamura
  • Article
    | Open Access

    Spinocerebellar ataxia type 2 (SCA2) is caused by polyglutamine repeats in the ATXN2 protein. Here the authors demonstrate that Staufen1, known to be an RNA-binding protein, interacts with ATXN2 and contributes to pathology in a mouse model of SCA2.

    • Sharan Paul
    • , Warunee Dansithong
    •  & Stefan M. Pulst
  • Article
    | Open Access

    Human development provides a roadmap for advancing pluripotent stem cell-based regenerative therapies. Here the authors mapped human skeletogenesis using RNA sequencing on 5 cell types from a single foetal stage as well as chondrocytes at 4 stages in vivo and 2 stages during in vitro differentiation.

    • Gabriel B. Ferguson
    • , Ben Van Handel
    •  & Denis Evseenko
  • Article
    | Open Access

    Tightly regulated promoters with strong inducibility and scalability are highly desirable for biological applications. Here the authors describe ‘Jungle Express’, a EilR repressor-based broad host system activated by cationic dyes.

    • Thomas L. Ruegg
    • , Jose H. Pereira
    •  & Michael P. Thelen
  • Article
    | Open Access

    AGO-PAR-CLIP is widely used for high-throughput miRNA target characterization. Here, the authors show that the previously neglected non-T-to-C clusters denote functional miRNA binding events, and develop microCLIP, a super learning framework that accurately detects miRNA interactions.

    • Maria D. Paraskevopoulou
    • , Dimitra Karagkouni
    •  & Artemis G. Hatzigeorgiou
  • Article
    | Open Access

    Brown adipose tissue (BAT) thermogenesis counteracts obesity and promotes metabolic health. The role of long non-coding RNAs (lncRNAs) in the regulation of this process is not well understood. Here the authors identify a maternally expressed lncRNA, H19, that increases BAT oxidative metabolism and energy expenditure.

    • Elena Schmidt
    • , Ines Dhaouadi
    •  & Jan-Wilhelm Kornfeld
  • Article
    | Open Access

    Chromatin dynamics is thought to play an important role in the maintenance of telomeres, yet how has remained poorly understood. Here the authors locally enrich heterochromatin protein 1α (HP1α) at human telomeres to provide insights into the crosstalk between epigenetic regulations and structural dynamics at the telomeres.

    • Tracy T. Chow
    • , Xiaoyu Shi
    •  & Elizabeth H. Blackburn
  • Article
    | Open Access

    Small RNA degrading nucleases (SDNs) can degrade short RNAs. Here the authors report the crystal structure of Arabidopsis SDN1 in complex with a single-stranded RNA, and provide new insight into 3′ end trimming mechanism of 3′ to 5′ riboexonucleases in the metabolism of various species of small RNAs.

    • Jiayi Chen
    • , Li Liu
    •  & Jinbiao Ma
  • Article
    | Open Access

    The effect of long noncoding RNAs (lncRNAs) on crop yield is unknown. Here, the authors show overexpression of a lncRNA, transcribed from the antisense strand of the previously discovered gene cluster LRK, can upregulate LRK genes’ expression, change histone modification status of LRK1, and increase rice grain yield.

    • Ying Wang
    • , Xiaojin Luo
    •  & Jinshui Yang
  • Article
    | Open Access

    Triple-negative breast cancer (TNBC) lacks prognostic and predictive markers. Here, the authors use phosphoproteomics to define kinases with distinct activity profiles in TNBC, demonstrating their prognostic value as well as their utility for simplifying TNBC classification and designing drug regimens.

    • Ivana Zagorac
    • , Sara Fernandez-Gaitero
    •  & Miguel Quintela-Fandino
  • Article
    | Open Access

    Suppression of gene expression due to aberrant promoter methylation contributes to organ fibrosis. Here, the authors couple a deactivated Cas9 to the TET3 catalytic domain to induce expression of four antifibrotic genes, and show that lentiviral-mediated delivery is effective in reducing kidney fibrosis in mouse models.

    • Xingbo Xu
    • , Xiaoying Tan
    •  & Michael Zeisberg
  • Article
    | Open Access

    Regulated secretion is an essential process that requires packing and maturation of cargo proteins in membranous secretory granules. Here, authors identify a gene, pgant9, that influences the glycosylation status of the secretory cargo as well as the structure of secretory granules within the Drosophila salivary gland.

    • Suena Ji
    • , Nadine L. Samara
    •  & Kelly G. Ten Hagen
  • Article
    | Open Access

    Histone marks regulate chromatin structure and function. Here the authors identify and characterize lysine benzoylation, a histone mark that can be modulated by sodium benzoate, a widely used chemical food preservative, associated with specific regulation of gene expression.

    • He Huang
    • , Di Zhang
    •  & Yingming Zhao
  • Article
    | Open Access

    Epidermal homeostasis is maintained by the activity of stem cells. Here, the authors show that deficiency of the transcription factor JunB leads to altered Notch signaling in stem cells, resulting in a cell fate switch and de novo formation of aberrant sebaceous glands, altered epidermal differentiation and impaired barrier function.

    • Karmveer Singh
    • , Emanuela Camera
    •  & Karin Scharffetter-Kochanek
  • Article
    | Open Access

    The molecular mechanisms leading to heart failure in patients with Duchenne muscular dystrophy are unclear. Here the authors show that NF-κB is activated in the heart of dystrophin-deficient mice and that its ablation rescues cardiac function through chromatin remodeling and activation of gene expression.

    • Jennifer M. Peterson
    • , David J. Wang
    •  & Denis C. Guttridge
  • Article
    | Open Access

    The co-transcriptional capping of transcripts synthesized by RNA Pol II is substantially more efficient than capping of free RNA, a process that has been shown to depend on CTD phosphorylation. Here the authors demonstrate that a CTD-independent mechanism functions in parallel with CTD-dependent processes to ensure efficient capping.

    • Melvin Noe Gonzalez
    • , Shigeo Sato
    •  & Ronald C. Conaway
  • Article
    | Open Access

    The role of Polycomb Repressive Complex 1 (PRC1) is well described in development. Here, the authors investigate canonical PRC1’s regulation of transcriptional programs in breast cancer where, in addition to its repressive function, it is also recruited to oncogenic active enhancers to regulate enhancer activity and chromatin accessibility.

    • Ho Lam Chan
    • , Felipe Beckedorff
    •  & Lluis Morey