Molecular biology articles within Nature Communications

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  • 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

  • Article
    | Open Access

    Mediator is a large multi-subunits complex essential to the regulation of transcription by RNA pol II. Here the authors report the crystal structure of MED23—one of the largest subunits of the complex together with MED1 and MED14—revealing a complex architecture and filling an important gap in the structural characterization of Mediator.

    • Didier Monté
    • , Bernard Clantin
    •  & Vincent Villeret

  • Review Article
    | Open Access

    Targeting DNA repair-deficient tumors is one of the most promising therapeutic strategies in cancer research; however, accurately predicting which tumors will respond can be a challenge. Here the authors present a review of the current state of knowledge in DNA repair deficiency across human cancers.

    • Jennifer Ma
    • , Jeremy Setton
    •  & Simon N. Powell

  • Article
    | Open Access

    INO80 chromatin remodeler plays important roles in transcription, DNA repair, recombination, and heterochromatin maintenance. Here the authors characterise the functional interplay between the actin-related proteins (Arps)  in INO80, showing that Arp8 and Arp4 module sense the DNA length separating nucleosomes and regulate nucleosome remodeling.

    • Sandipan Brahma
    • , Mzwanele Ngubo
    •  & Blaine Bartholomew

  • Article
    | Open Access

    Accurate detection of TADs requires ultra-deep sequencing and sophisticated normalisation procedures, which limits the analysis of Hi-C data. Here the authors develop a normalisation-free method to decode the domains of chromosomes (deDoc) that utilizes structural entropy to predict TADs with ultra-low sequencing data.

    • Angsheng Li
    • , Xianchen Yin
    •  & Zhihua Zhang

  • Article
    | Open Access

    The circadian clock proteins KaiA, KaiB, and KaiC reconstitute a circa-24 h oscillation of KaiC phosphorylation in vitro. Here the authors use high-speed atomic force microscopy to visualize in real time and quantify the dynamic interactions of KaiA with KaiC on the sub-second timescale to discover mechanisms of oscillatory resilience.

    • Tetsuya Mori
    • , Shogo Sugiyama
    •  & Toshio Ando

  • Article
    | Open Access

    PARP1 and PARP2 of the PARP family enzymes are involved in DNA damage response. Here the authors report PARP2 activation mechanisms and its role in the formation of branched poly(ADP-ribose) chains in response to DNA damage.

    • Qian Chen
    • , Muzaffer Ahmad Kassab
    •  & Xiaochun Yu

  • Article
    | Open Access

    Epigenetic modifications are a key contributor to cell identity, and their propagation is crucial for proper development. Here the authors use a super-resolution microscopy approach to reveal how histone variants are faithfully transmitted during genome duplication, and reveal an important role for the histone chaperone ASF1 in the redistribution of parental histones.

    • Camille Clément
    • , Guillermo A. Orsi
    •  & Geneviève Almouzni

  • Article
    | Open Access

    The 3D organization of chromosomes within the nuclear space is important for biological functions. Here the authors model chromosomes as self-avoiding copolymers with distinct epigenetic states, and show that the features of experimentally generated contact maps can be reproduced and their dynamics predicted.

    • Guang Shi
    • , Lei Liu
    •  & D. Thirumalai

  • Article
    | Open Access

    Recent studies have identified a number of oncogenic histone point mutations in different cancers. Here the authors provide evidence that H3.3 G34R substitution mutation, which is found in paediatric gliomas, causes changes in H3K9me3 and H3K36me3 by interfering with the KDM4 family of K9/K36 demethylases.

    • Hsiao P. J. Voon
    • , Maheshi Udugama
    •  & Lee H. Wong

  • Article
    | Open Access

    HLX transcription factor regulates haematopoietic stem and progenitor cell (HSPC) differentiation and is overexpressed in acute myeloid leukemia. Here the authors show that HLX overexpression leads to myeloid differentiation block in zebrafish and human HSPCs by direct regulation of metabolic pathways.

    • Indre Piragyte
    • , Thomas Clapes
    •  & Eirini Trompouki

  • Article
    | Open Access

    AND-1, the vertebrate orthologue of Ctf4, is a critical player during DNA replication and for maintenance of genome integrity. Here the authors use a conditional AND-1 depletion system in avian DT40 cells to reveal the consequences of the lack of AND-1 on cell proliferation and DNA replication.

    • Takuya Abe
    • , Ryotaro Kawasumi
    •  & Dana Branzei

  • Article
    | Open Access

    Splicing of the telomerase transcript, hTERT, can be altered in cancer cells. Here the authors report NOVA1, as a splicing regulator that directly interacts with hTERT pre-mRNA enhancing the number of full-length transcripts and thus telomerase activity in lung cancer cells.

    • Andrew T. Ludlow
    • , Mandy Sze Wong
    •  & Jerry W. Shay

  • Article
    | Open Access

    YAP is a transcriptional co-activator downstream of Hippo pathway that displays oncogenic but also tumour suppressive functions. Here, the authors perform an unbiased genome wide CRISPR screen and identify Trichorhinophalangeal syndrome 1 (TRPS1) that represses YAP/TEAD activity independently of Hippo pathway in breast cancer.

    • Dana Elster
    • , Marie Tollot
    •  & Björn von Eyss

  • Article
    | Open Access

    Undesired off-target effects can hamper the use of CRISPR-Cas9 in therapeutic applications. Here the authors use a directed evolution approach to develop Sniper-Cas9 which combines high specificity with no loss of on-target activity.

    • Jungjoon K. Lee
    • , Euihwan Jeong
    •  & Jin-Soo Kim

  • Article
    | Open Access

    Single nuclei RNA-seq has been used to characterize transcriptional signature of environment-related activity in cells of the dentate gyrus. Here the authors use this approach to show that whether a neuron will be reactivated in response to re-exposure to a previous environment can be predicted by its transcriptional signature.

    • Baptiste N. Jaeger
    • , Sara B. Linker
    •  & Fred H. Gage

  • Article
    | Open Access

    Binding of eIF4E to the 5′ cap of mRNAs is a key early step in canonical translation initiation, but the requirement for eIF4E is not universal. Here the authors show that the eIF4G homolog DAP5 interacts with eIF3 to promote cap-dependent translation of a significant number of mRNA in an eIF4E-independent manner.

    • Columba de la Parra
    • , Amanda Ernlund
    •  & Robert J. Schneider

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