Molecular biology

  • Article | | open

    Membrane elongation is fundamental to autophagy and is controlled by an ubiquitin-conjugating cascade orchestrated by ATG16L1. Here, the authors identify that the E3 ligase Gigaxonin regulates autophagosome formation by controlling ATG16L1 turnover.

    • Aurora Scrivo
    • , Patrice Codogno
    •  & Pascale Bomont
  • Article | | open

    SecB homologs can be associated with stress-responsive type II toxin–antitoxin (TA) systems and form tripartite toxin-antitoxin-chaperone systems (TAC). Here the authors provide structural insights into TACs by presenting the crystal structure of the M. tuberculosis TA-associated SecB chaperone in complex with the C-terminal ChAD (chaperone addiction) extension of the antitoxin HigA1.

    • Valérie Guillet
    • , Patricia Bordes
    • , Cécile Bon
    • , Julien Marcoux
    • , Virginie Gervais
    • , Ambre Julie Sala
    • , Suzana Dos Reis
    • , Nawel Slama
    • , Israel Mares-Mejía
    • , Anne-Marie Cirinesi
    • , Laurent Maveyraud
    • , Pierre Genevaux
    •  & Lionel Mourey
  • Article | | open

    Serine/threonine phosphatases such as PP1 associate with a large array of subunit proteins, such as ASPP (apoptosis-stimulating protein of p53) to achieve selective targeting. Here authors solved the crystal structure of the human ASPP2/PP1 complex and explain how ASPP2 can distinguish between PP1 isoforms.

    • M. Teresa Bertran
    • , Stéphane Mouilleron
    • , Yanxiang Zhou
    • , Rakhi Bajaj
    • , Federico Uliana
    • , Ganesan Senthil Kumar
    • , Audrey van Drogen
    • , Rebecca Lee
    • , Jennifer J. Banerjee
    • , Simon Hauri
    • , Nicola O’Reilly
    • , Matthias Gstaiger
    • , Rebecca Page
    • , Wolfgang Peti
    •  & Nicolas Tapon
  • Article | | open

    SUMOylation is known to regulate androgen receptor (AR) activity in cultured cells. Here, using SUMOylation-deficient AR knock-in mice, the authors demonstrate that SUMOylation is required for AR-related gene expression specifically in the epididymal tissues, but not the testis.

    • Fu-Ping Zhang
    • , Marjo Malinen
    • , Arfa Mehmood
    • , Tiina Lehtiniemi
    • , Tiina Jääskeläinen
    • , Einari A. Niskanen
    • , Hanna Korhonen
    • , Asta Laiho
    • , Laura L. Elo
    • , Claes Ohlsson
    • , Noora Kotaja
    • , Matti Poutanen
    • , Petra Sipilä
    •  & Jorma J. Palvimo
  • Article | | open

    Viruses can encode genes that regulate the host's translational machinery to their advantage. Here, the authors show that viruses encode ribosomal proteins that can be incorporated into the host’s ribosome and may affect translation.

    • Carolina M. Mizuno
    • , Charlotte Guyomar
    • , Simon Roux
    • , Régis Lavigne
    • , Francisco Rodriguez-Valera
    • , Matthew B. Sullivan
    • , Reynald Gillet
    • , Patrick Forterre
    •  & Mart Krupovic
  • Article | | open

    Here, Depledge et al. use nanopore arrays for direct RNA sequencing to profile the HSV-1 transcriptome in productively infected cells. Sequencing of individual RNAs reveals a highly complex viral transcriptome including mRNAs encoding new viral fusion proteins derived by read-through transcription.

    • Daniel P. Depledge
    • , Kalanghad Puthankalam Srinivas
    • , Tomohiko Sadaoka
    • , Devin Bready
    • , Yasuko Mori
    • , Dimitris G. Placantonakis
    • , Ian Mohr
    •  & Angus C. Wilson
  • Article | | open

    Few approaches for targeted manipulation of the epigenome are available in plants. Here, the authors adapt the dCas9-SunTag system to engineer targeted gene activation and site-specific manipulation of DNA methylation in Arabidopsis.

    • Ashot Papikian
    • , Wanlu Liu
    • , Javier Gallego-Bartolomé
    •  & Steven E. Jacobsen
  • Article | | open

    Homology directed repair of meiotic double-strand breaks functions via recruitment and assembly of strand-exchange proteins called recombinases. Here the authors reveal and characterize a BRCA2 interactor regulating meiotic recombinases that localizes to chromosomal axes and facilitates the repair of meiotic DSBs.

    • Jingjing Zhang
    • , Yasuhiro Fujiwara
    • , Shohei Yamamoto
    •  & Hiroki Shibuya
  • Article | | open

    No structural data have been available for RNA polymerase holoenzymes or transcription initiation complexes that contain extracytoplasmic σ factors. Here the authors report the crystal structures of transcription initiation complexes comprising Mycobacterium tuberculosis RNA polymerase, extracytoplasmic σ factor σL and promoter DNA.

    • Wei Lin
    • , Sukhendu Mandal
    • , David Degen
    • , Min Sung Cho
    • , Yu Feng
    • , Kalyan Das
    •  & Richard H. Ebright
  • Article | | open

    The antitermination factor RfaH adopts two functional states where its C-terminal domain is folded either as an α-helical hairpin or β-barrel. Here the authors employ solution state NMR measurements to show that the C-terminal domain transforms into the β-barrel only upon binding to the elongation complex and refolds back after dissociation.

    • Philipp Konrad Zuber
    • , Kristian Schweimer
    • , Paul Rösch
    • , Irina Artsimovitch
    •  & Stefan H. Knauer
  • Article | | open

    Transcription is globally repressed in early stage of embryo development, but a set of genes including pri-miR-430 and zinc finger genes is known to escape the repression. Here the authors image the very first transcriptional activities in the living zebra fish embryo, demonstrating a cell cycle-coordinated polymerase II transcription compartment.

    • Yavor Hadzhiev
    • , Haseeb K. Qureshi
    • , Lucy Wheatley
    • , Ledean Cooper
    • , Aleksandra Jasiulewicz
    • , Huy Van Nguyen
    • , Joseph W. Wragg
    • , Divyasree Poovathumkadavil
    • , Sascha Conic
    • , Sarah Bajan
    • , Attila Sik
    • , György Hutvàgner
    • , Làszlò Tora
    • , Agnieszka Gambus
    • , John S. Fossey
    •  & Ferenc Müller
  • Article | | open

    Ubiquitination may control protein stability or function. Here the authors show that an ubiquitination enzyme, Hectd3, ubiquitinates Stat3 and Malt1 to modulate their function but not degradation in T cells, and thereby promoting the differentiation of pathogenic Th17 cells and susceptibility to a mouse model of multiple sclerosis.

    • Jonathan J. Cho
    • , Zhiwei Xu
    • , Upasana Parthasarathy
    • , Theodore T. Drashansky
    • , Eric Y. Helm
    • , Ashley N. Zuniga
    • , Kyle J. Lorentsen
    • , Samira Mansouri
    • , Joshua Y. Cho
    • , Mariola J. Edelmann
    • , Duc M. Duong
    • , Torben Gehring
    • , Thomas Seeholzer
    • , Daniel Krappmann
    • , Mohammad N. Uddin
    • , Danielle Califano
    • , Rejean L. Wang
    • , Lei Jin
    • , Hongmin Li
    • , Dongwen Lv
    • , Daohong Zhou
    • , Liang Zhou
    •  & Dorina Avram
  • Article | | open

    Cancer cells respond differently to inhibitors of Poly (ADP-ribose) polymerase. Here the authors reveal that ovarian cancer cells with higher cellular NADP+ levels are more sensitive to clinically relevant PARP1 inhibitors and show that NADP+ act as an endogenous inhibitor of PARP enzymes.

    • Chunjing Bian
    • , Chao Zhang
    • , Tao Luo
    • , Aditi Vyas
    • , Shih-Hsun Chen
    • , Chao Liu
    • , Muzaffer Ahmad Kassab
    • , Ying Yang
    • , Mei Kong
    •  & Xiaochun Yu
  • Article | | open

    How the chromosome passenger complex (CPC) phosphorylates the kinetochores that can be a micron away to control mitotic events is unknown. Here the authors find that the CPC directly binds microtubules near inner centromeres, which controls its ability to phosphorylate kinetochores independently of tension generated by kinetochore microtubule attachments.

    • Prasad Trivedi
    • , Anatoly V. Zaytsev
    • , Maxim Godzi
    • , Fazly I. Ataullakhanov
    • , Ekaterina L. Grishchuk
    •  & P. Todd Stukenberg
  • Article | | open

    Cryo-electron microscopy can determine the structure but not the nanomechanics of biological matter. Here the authors combine force spectroscopy in cryogenic conditions with computer simulations to characterize the properties of DNA simultaneously down to the sub-nm level.

    • Rémy Pawlak
    • , J. G. Vilhena
    • , Antoine Hinaut
    • , Tobias Meier
    • , Thilo Glatzel
    • , Alexis Baratoff
    • , Enrico Gnecco
    • , Rubén Pérez
    •  & Ernst Meyer
  • Article | | open

    We know a large number of risk SNPs for schizophrenia, but little about how these SNPs contribute to the disorder. Here, the authors use functional genomics to identify risk SNPs that disrupt transcription factor binding and validate the regulatory effects of the transcription factor binding-disrupting SNPs.

    • Yongxia Huo
    • , Shiwu Li
    • , Jiewei Liu
    • , Xiaoyan Li
    •  & Xiong-Jian Luo
  • Article | | open

    Many 2-Cystein Peroxiredoxins (Prx) can either function as peroxidases or chaperones when exposed to stress. Here the authors present the structures of Leishmania infantum mitochondrial Prx alone and with a bound model client protein, use crosslinking to reveal interaction regions that stabilize the bound client, and provide insights into the mechanism by which Prx’s adopt chaperone activity.

    • Filipa Teixeira
    • , Eric Tse
    • , Helena Castro
    • , Karl A. T. Makepeace
    • , Ben A. Meinen
    • , Christoph H. Borchers
    • , Leslie B. Poole
    • , James C. Bardwell
    • , Ana M. Tomás
    • , Daniel R. Southworth
    •  & Ursula Jakob
  • Article | | open

    Capicua (CIC) is a tumour suppressor in oligodendroglioma. Here, the authors show that ERK activation mediates CIC regulation via ubiquitination and degradation by PJA1 and a degradation resistant form of CIC enhances efficacy of ERK inhibition in glioblastoma.

    • Severa Bunda
    • , Pardeep Heir
    • , Julie Metcalf
    • , Annie Si Cong Li
    • , Sameer Agnihotri
    • , Stefan Pusch
    • , Mamatjan Yasin
    • , Mira Li
    • , Kelly Burrell
    • , Sheila Mansouri
    • , Olivia Singh
    • , Mark Wilson
    • , Amir Alamsahebpour
    • , Romina Nejad
    • , Bethany Choi
    • , David Kim
    • , Andreas von Deimling
    • , Gelareh Zadeh
    •  & Kenneth Aldape
  • Article | | open

    A fundamental step in membrane protein biogenesis is their integration into the lipid bilayer with a defined orientation of each transmembrane segment. Here, the authors show that mutations in connexin 32 can cause failures in membrane integration which is detected by the ER chaperone machinery.

    • João P. L. Coelho
    • , Matthias Stahl
    • , Nicolas Bloemeke
    • , Kevin Meighen-Berger
    • , Carlos Piedrafita Alvira
    • , Zai-Rong Zhang
    • , Stephan A. Sieber
    •  & Matthias J. Feige
  • Article | | open

    Insulin-related gene (Insig) negatively regulates hepatic fatty acid synthesis, a process involved in development of non-alcoholic fatty liver disease (NAFLD). Here, the authors show that AMPK activation by metformin promotes Insig phosphorylation, stabilizing it and inhibiting lipogenic gene expression. This is protective against steatosis in diabetic mice.

    • Yamei Han
    • , Zhimin Hu
    • , Aoyuan Cui
    • , Zhengshuai Liu
    • , Fengguang Ma
    • , Yaqian Xue
    • , Yuxiao Liu
    • , Feifei Zhang
    • , Zehua Zhao
    • , Yanyan Yu
    • , Jing Gao
    • , Chun Wei
    • , Jingya Li
    • , Jing Fang
    • , Jia Li
    • , Jian-Gao Fan
    • , Bao-Liang Song
    •  & Yu Li
  • Article | | open

    24-nt phased siRNA (phasiRNA) regulate reproduction in grasses, yet are absent from Arabidopsis, and were thought to be monocot-specific. Here, Xia et al. show that 24-nt phasiRNAs are in fact broadly distributed among eudicots and are consistently enriched during meiosis, despite possibly arising from distinct biogenesis pathways.

    • Rui Xia
    • , Chengjie Chen
    • , Suresh Pokhrel
    • , Wuqiang Ma
    • , Kun Huang
    • , Parth Patel
    • , Fuxi Wang
    • , Jing Xu
    • , Zhongchi Liu
    • , Jianguo Li
    •  & Blake C. Meyers
  • Article | | open

    PTEN is a lipid phosphatase that functions as a dose-dependent tumor suppressor through the PI3K/AKT pathway. Here the authors describe a signaling feedback mechanism where PTEN stability is regulated through transcriptional upregulation of X-linked ubiquitin-specific protease 11 (USP11) via the PI3K/FOXO pathway.

    • Mi Kyung Park
    • , Yixin Yao
    • , Weiya Xia
    • , Stephanie Rebecca Setijono
    • , Jae Hwan Kim
    • , Isabelle K. Vila
    • , Hui-Hsuan Chiu
    • , Yun Wu
    • , Enrique González Billalabeitia
    • , Min Gyu Lee
    • , Robert G. Kalb
    • , Mien-Chie Hung
    • , Pier Paolo Pandolfi
    • , Su Jung Song
    •  & Min Sup Song
  • Article | | open

    Nuclear envelopathies are a group of diseases caused by genetic mutations in essential nuclear envelope genes. Here, the authors report a nuclear envelopathy with a homozygous nonsense variant in TOR1AIP1 which leads to changes in the nuclear morphology including large nuclear-spanning channels in patients’ fibroblasts.

    • Boris Fichtman
    • , Fadia Zagairy
    • , Nitzan Biran
    • , Yiftah Barsheshet
    • , Elena Chervinsky
    • , Ziva Ben Neriah
    • , Avraham Shaag
    • , Michael Assa
    • , Orly Elpeleg
    • , Amnon Harel
    •  & Ronen Spiegel
  • Article | | open

    Zinc ions (Zn2+) are imported by Golgi-resident transporters but the function of zinc in the early secretory pathway has remained unknown. Here the authors find that Zn2+ regulates protein quality control in the early secretory pathway by demonstrating that the pH-sensitive chaperone ERp44 binds Zn2+ and solving the Zn2+-bound ERp44 structure.

    • Satoshi Watanabe
    • , Yuta Amagai
    • , Sara Sannino
    • , Tiziana Tempio
    • , Tiziana Anelli
    • , Manami Harayama
    • , Shoji Masui
    • , Ilaria Sorrentino
    • , Momo Yamada
    • , Roberto Sitia
    •  & Kenji Inaba
  • Article | | open

    Kinetochore function depends on H4K20 monomethylation in centromeric nucleosomes but the underlying mechanism is unclear. Here, the authors provide evidence that the centromere-specific nucleosome subunit CENP-A facilitates H4K20 methylation by enabling a conformational change of the H4 N-terminal tail.

    • Yasuhiro Arimura
    • , Hiroaki Tachiwana
    • , Hiroki Takagi
    • , Tetsuya Hori
    • , Hiroshi Kimura
    • , Tatsuo Fukagawa
    •  & Hitoshi Kurumizaka
  • Article | | open

    The TERB1-TERB2-MAJIN complex mediates the attachment of telomeres to the nuclear envelope. Here the authors present the crystal structures of the human TERB1-TERB2 and TERB2-MAJIN subcomplexes and show that Terb2 mutations, which abolish complex formation cause aberrant homologous pairing and disordered synapsis in mouse.

    • Yan Wang
    • , Yanyan Chen
    • , Juan Chen
    • , Lijun Wang
    • , Leitong Nie
    • , Juanjuan Long
    • , Haishuang Chang
    • , Jian Wu
    • , Chenhui Huang
    •  & Ming Lei
  • Article | | open

    The genomic locations that can be targeted for editing by CRISPR are limited by the presence of the nuclease-specific PAM sequence. Here, the authors show PAM recognition can be expanded by replacing the key region in the PAM interaction domain of SaCas9 with the corresponding region of SaCas9 orthologs.

    • Dacheng Ma
    • , Zhimeng Xu
    • , Zhaoyu Zhang
    • , Xi Chen
    • , Xiangzhi Zeng
    • , Yiyang Zhang
    • , Tingyue Deng
    • , Mengfei Ren
    • , Zheng Sun
    • , Rui Jiang
    •  & Zhen Xie
  • Article | | open

    Ribosome-associated quality control (RQC) pathways monitor and respond to stalling of the translating ribosome. Here the authors show that the ribosome associated RQC factor Hel2/ZNF598, an E3 ubiquitin ligase, generally interacts with mRNAs in the vicinity of stop codons.

    • Marie-Luise Winz
    • , Lauri Peil
    • , Tomasz W. Turowski
    • , Juri Rappsilber
    •  & David Tollervey
  • Article | | open

    The role of mesencephalic astrocyte-derived neurotrophic factor (MANF) in maintenance of protein folding homeostasis inside the ER has remained unclear. Here the authors determine the structure of the complex between MANF and the ER-localized chaperone BiP and provide evidence that MANF serves as an anti-nucleotide exchange factor for BiP.

    • Yahui Yan
    • , Claudia Rato
    • , Lukas Rohland
    • , Steffen Preissler
    •  & David Ron
  • Article | | open

    Rix7 is a type II AAA-ATPase that is required for the assembly of the large ribosomal subunit. Here the authors present the 4.5 Å cryo-EM structure of the Rix7 homohexamer with a polypeptide fragment bound in its central channel and provide insights into the function of Rix7 as a molecular unfoldase.

    • Yu-Hua Lo
    • , Mack Sobhany
    • , Allen L. Hsu
    • , Brittany L. Ford
    • , Juno M. Krahn
    • , Mario J. Borgnia
    •  & Robin E. Stanley
  • Article | | open

    The exon junction complex (EJC) has been identified as functioning as a post-transcriptional gene regulator. Here the authors reveal that the complex also plays a part in the regulation of transcription by regulating the release of Pol II pausing into transcription elongation.

    • Junaid Akhtar
    • , Nastasja Kreim
    • , Federico Marini
    • , Giriram Mohana
    • , Daniel Brüne
    • , Harald Binder
    •  & Jean-Yves Roignant
  • Article | | open

    Large protein complexes and ribonucleoprotein particles (RNPs) such as pre-ribosomes are transported from the nucleus to the cytoplasm through the nuclear pore complex (NPC). Here the authors use ultrafast freezing and electron tomography to catch snapshots of native RNPs crossing the NPC and estimate their transit time using a probabilistic model.

    • Franck Delavoie
    • , Vanessa Soldan
    • , Dana Rinaldi
    • , Jean-Yves Dauxois
    •  & Pierre-Emmanuel Gleizes
  • Article | | open

    Membraneless compartments have been theorized to be prebiotic micro-compartments as they spontaneously encapsulate RNA and proteins. Here, the authors report membraneless compartments can enhance RNA chemistries, affecting template directed RNA polymerization and stimulating nucleic acid enzymes.

    • Raghav R. Poudyal
    • , Rebecca M. Guth-Metzler
    • , Andrew J. Veenis
    • , Erica A. Frankel
    • , Christine D. Keating
    •  & Philip C. Bevilacqua
  • Article | | open

    Mammalian transcription factors (TFs) differ broadly in their DNA binding properties. Here authors quantify mitotic chromosome binding (MCB) of 501 TFs and suggest that MCB can be used as a proxy for non-specific TF-DNA interactions that regulate TF search for specific genomic sites.

    • Mahé Raccaud
    • , Elias T. Friman
    • , Andrea B. Alber
    • , Harsha Agarwal
    • , Cédric Deluz
    • , Timo Kuhn
    • , J. Christof M. Gebhardt
    •  & David M. Suter
  • Article | | open

    IRSp53 is a key regulator of filopodia formation and cell migration. Here, the authors elucidate a mechanism of phosphorylation-dependent inhibition of IRSp53 by 14-3-3, which impedes the interactions of IRSp53 with membranes and downstream cytoskeletal effectors.

    • David J. Kast
    •  & Roberto Dominguez
  • Article | | open

    Heterogeneity in gene expression and epigenetic states exists across individual cells. Here, the authors develop scCAT-seq, a technique for simultaneously performing ATAC-seq and RNA-seq within the same single cell.

    • Longqi Liu
    • , Chuanyu Liu
    • , Andrés Quintero
    • , Liang Wu
    • , Yue Yuan
    • , Mingyue Wang
    • , Mengnan Cheng
    • , Lizhi Leng
    • , Liqin Xu
    • , Guoyi Dong
    • , Rui Li
    • , Yang Liu
    • , Xiaoyu Wei
    • , Jiangshan Xu
    • , Xiaowei Chen
    • , Haorong Lu
    • , Dongsheng Chen
    • , Quanlei Wang
    • , Qing Zhou
    • , Xinxin Lin
    • , Guibo Li
    • , Shiping Liu
    • , Qi Wang
    • , Hongru Wang
    • , J. Lynn Fink
    • , Zhengliang Gao
    • , Xin Liu
    • , Yong Hou
    • , Shida Zhu
    • , Huanming Yang
    • , Yunming Ye
    • , Ge Lin
    • , Fang Chen
    • , Carl Herrmann
    • , Roland Eils
    • , Zhouchun Shang
    •  & Xun Xu
  • Article | | open

    The origin and physiological significance of lipid droplets (LDs) in the nucleus is not clear. Here authors show that nucleoplasmic LDs in hepatocytes are derived from apolipoprotein B (ApoB)-free lumenal LDs and constitute a feedback mechanism to regulate PC synthesis in accordance with ER stress.

    • Kamil Sołtysik
    • , Yuki Ohsaki
    • , Tsuyako Tatematsu
    • , Jinglei Cheng
    •  & Toyoshi Fujimoto
  • Article | | open

    The establishment of functional vasculatures requires the specification of newly formed vessels into veins and arteries. Here, Neal et al. use a combination of genetic approaches in mice and zebrafish to show that BMP signalling, via ALK3 and SMAD1/5, is required for venous specification during blood vessel development.

    • Alice Neal
    • , Svanhild Nornes
    • , Sophie Payne
    • , Marsha D. Wallace
    • , Martin Fritzsche
    • , Pakavarin Louphrasitthiphol
    • , Robert N. Wilkinson
    • , Kira M. Chouliaras
    • , Ke Liu
    • , Karen Plant
    • , Radhika Sholapurkar
    • , Indrika Ratnayaka
    • , Wiebke Herzog
    • , Gareth Bond
    • , Tim Chico
    • , George Bou-Gharios
    •  & Sarah De Val
  • Article | | open

    The inactive X chromosome (Xi) is a model for establishment and maintenance of repressed chromatin and the function of polycomb repressive complexes. Here the authors show that Xi transiently relocates from the nuclear periphery during replication in a CIZ1-dependent manner, which plays a role in maintaining PRC-mediated repressed chromatin.

    • Emma R. Stewart
    • , Robert M. L. Turner
    • , Katherine Newling
    • , Rebeca Ridings-Figueroa
    • , Victoria Scott
    • , Peter D. Ashton
    • , Justin F. X. Ainscough
    •  & Dawn Coverley
  • Article | | open

    Genetic logic devices allow the host cell to incorporate multiple inputs to determine output behaviour. Here the authors provide a framework for engineering reliable recombinase-based devices and demonstrate 4-input logic in a multicellular system.

    • Sarah Guiziou
    • , Pauline Mayonove
    •  & Jerome Bonnet
  • Article | | open

    Designing interfaces that can induce protein-protein interactions is a challenging problem. Here the authors show that a five amino acid sequence known to mediate domain swapping in cystatins can drive oligomerization when grafted onto functionally and structurally unrelated host proteins, providing a simple approach to the design of protein assemblies.

    • Neha Nandwani
    • , Parag Surana
    • , Hitendra Negi
    • , Nahren M. Mascarenhas
    • , Jayant B. Udgaonkar
    • , Ranabir Das
    •  & Shachi Gosavi
  • Article | | open

    Multiple morphological abnormalities of the sperm flagella (MMAF) is a cause of male infertility. Here the authors identify homozygous nonsense mutations of the glutamine rich 2 (QRICH2) gene in two MMAF patients from 2 consanguineous families and show using QRICH2 knockout mice that the protein is required for sperm flagellar formation and motility.

    • Ying Shen
    • , Feng Zhang
    • , Fuping Li
    • , Xiaohui Jiang
    • , Yihong Yang
    • , Xiaoliang Li
    • , Weiyu Li
    • , Xiang Wang
    • , Juan Cheng
    • , Mohan Liu
    • , Xueguang Zhang
    • , Guiping Yuan
    • , Xue Pei
    • , Kailai Cai
    • , Fengyun Hu
    • , Jianfeng Sun
    • , Lanzhen Yan
    • , Li Tang
    • , Chuan Jiang
    • , Wenling Tu
    • , Jinyan Xu
    • , Haojuan Wu
    • , Weiqi Kong
    • , Shuying Li
    • , Ke Wang
    • , Kai Sheng
    • , Xudong Zhao
    • , Huanxun Yue
    • , Xiaoyu Yang
    •  & Wenming Xu
  • Article | | open

    The delivery of single therapeutic microRNAs in brain cancers is challenging. Here, the authors engineer three neuronal microRNAs (miR-124, 128 and 137) into a cluster that, targeting oncogenic chromatin repressors, increases survival of GBM-bearing mice when combined with chemotherapy.

    • Vivek Bhaskaran
    • , Michal O. Nowicki
    • , Mahmoud Idriss
    • , Miguel A. Jimenez
    • , Gianmarco Lugli
    • , Josie L. Hayes
    • , Ahmad Bakur Mahmoud
    • , Rachel E. Zane
    • , Carmela Passaro
    • , Keith L. Ligon
    • , Daphne Haas-Kogan
    • , Agnieszka Bronisz
    • , Jakub Godlewski
    • , Sean E. Lawler
    • , E. Antonio Chiocca
    •  & Pierpaolo Peruzzi
  • Article | | open

    Transcription factors of the AP-1 family can play diverse roles despite recognizing the same DNA sequence. Here the authors investigate the DNA binding activities of AP-1 members in mouse macrophages and apply a machine learning approach to identify motifs predicted to drive factor-specific binding profiles.

    • Gregory J. Fonseca
    • , Jenhan Tao
    • , Emma M. Westin
    • , Sascha H. Duttke
    • , Nathanael J. Spann
    • , Tobias Strid
    • , Zeyang Shen
    • , Joshua D. Stender
    • , Mashito Sakai
    • , Verena M. Link
    • , Christopher Benner
    •  & Christopher K. Glass
  • Article | | open

    ER stress and UPR are implicated in various cancers. Here, the authors show that one of the canonical UPR pathways, IRE1α-XBP1 regulates c-MYC signaling to promote prostate tumorigenesis, and pharmacological inhibition of IRE1α with MKC8866 inhibits prostate cancer growth and synergizes with clinically used prostate cancer drugs.

    • Xia Sheng
    • , Hatice Zeynep Nenseth
    • , Su Qu
    • , Omer F. Kuzu
    • , Turid Frahnow
    • , Lukas Simon
    • , Stephanie Greene
    • , Qingping Zeng
    • , Ladan Fazli
    • , Paul S. Rennie
    • , Ian G. Mills
    • , Håvard Danielsen
    • , Fabian Theis
    • , John B. Patterson
    • , Yang Jin
    •  & Fahri Saatcioglu
  • Article | | open

    Hippo signaling leads to the phosphorylation of the key transcriptional effector, Yap/Yki, although how Yap/Yki stability is regulated has remained unclear. Here, Sun et al. identify HAUSP/Usp7 as a conserved and clinically relevant regulator of the Hippo pathway that increases Yap/Yki stability.

    • Xiaohan Sun
    • , Yan Ding
    • , Meixiao Zhan
    • , Yan Li
    • , Dongqing Gao
    • , Guiping Wang
    • , Yang Gao
    • , Yong Li
    • , Shian Wu
    • , Ligong Lu
    • , Qingxin Liu
    •  & Zizhang Zhou
  • Article | | open

    The connection between DNA replication timing and changes that occur to the epigenome in cancer are still poorly understood. Here, the authors perform Repli-Seq and integrated epigenome analyses and find that genomic regions that undergo long-range epigenetic deregulation in prostate cancer also show concordant differences in replication timing.

    • Qian Du
    • , Saul A. Bert
    • , Nicola J. Armstrong
    • , C. Elizabeth Caldon
    • , Jenny Z. Song
    • , Shalima S. Nair
    • , Cathryn M. Gould
    • , Phuc-Loi Luu
    • , Timothy Peters
    • , Amanda Khoury
    • , Wenjia Qu
    • , Elena Zotenko
    • , Clare Stirzaker
    •  & Susan J. Clark
  • Article | | open

    The DNA ligase of African swine fever virus is one of the most error-prone ligases identified to date, but underlying molecular details are lacking. Here, Chen et al. report four AsfvLIG:DNA structures and identify a unique N-terminal domain and four unique active site residues that are crucial for its catalytic efficiency.

    • Yiqing Chen
    • , Hehua Liu
    • , Chun Yang
    • , Yanqing Gao
    • , Xiang Yu
    • , Xi Chen
    • , Ruixue Cui
    • , Lina Zheng
    • , Suhua Li
    • , Xuhang Li
    • , Jinbiao Ma
    • , Zhen Huang
    • , Jixi Li
    •  & Jianhua Gan