The EMBO Journal

Cover image for Vol. 34 Issue 10

Early View (Online Version of Record published before inclusion in an issue)

Online ISSN: 1460-2075

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  1. 1 - 36
  1. Articles

    1. Loss of MT1-MMP causes cell senescence and nuclear defects which can be reversed by retinoic acid

      Ana Gutiérrez-Fernández, Clara Soria-Valles, Fernando G Osorio, Jesús Gutiérrez-Abril, Cecilia Garabaya, Alina Aguirre, Antonio Fueyo, María Soledad Fernández-García, Xose S Puente and Carlos López-Otín

      Article first published online: 19 MAY 2015 | DOI: 10.15252/embj.201490594

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      Alterations in the extracellular matrix caused by loss of protease MT1-MMP lead to cellular senescence, nuclear lamina abnormalities, and features of premature ageing that can be rescued by treatment with retinoic acid.

    2. Reciprocal regulation of amino acid import and epigenetic state through Lat1 and EZH2

      Stephen G Dann, Michael Ryskin, Anthony M Barsotti, Jonathon Golas, Celine Shi, Miriam Miranda, Christine Hosselet, Luanna Lemon, Judy Lucas, Maha Karnoub, Fang Wang, Jeremy S Myers, Scott J Garza, Maximillian T Follettie, Kenneth G Geles, Anke Klippel, Robert A Rollins and Valeria R Fantin

      Article first published online: 15 MAY 2015 | DOI: 10.15252/embj.201488166

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      The amino acid transporter Lat1 increases cellular S-adenosylmethionine concentrations and thereby EZH2 activity, and this dictates the differentiation state of cancer cells and tumour growth.

    3. You have full text access to this OnlineOpen article
      TUT7 controls the fate of precursor microRNAs by using three different uridylation mechanisms

      Boseon Kim, Minju Ha, Luuk Loeff, Hyeshik Chang, Dhirendra K Simanshu, Sisi Li, Mohamed Fareh, Dinshaw J Patel, Chirlmin Joo and V Narry Kim

      Article first published online: 15 MAY 2015 | DOI: 10.15252/embj.201590931

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      Uridylation of miRNA precursors can either stimulate processing or trigger RNA degradation. This study shows how RNA overhang structure and the mode of TUTase binding facilitate differential uridylation of specific precursor types.

    4. Not4-dependent translational repression is important for cellular protein homeostasis in yeast

      Steffen Preissler, Julia Reuther, Miriam Koch, Annika Scior, Michael Bruderek, Tancred Frickey and Elke Deuerling

      Article first published online: 13 MAY 2015 | DOI: 10.15252/embj.201490194

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      Not4, a component of the CCR4-NOT complex, triggers translational repression of mRNAs carrying transiently stalled ribosomes and contributes to the maintenance of protein homeostasis during cellular stress.

  2. Have you seen?

    1. Poised for action: USP18 restrains microglial activation in the white matter

      Kazuyuki Takata and Florent Ginhoux

      Article first published online: 13 MAY 2015 | DOI: 10.15252/embj.201591899

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      Dedicated mechanisms actively maintain CNS macrophages in a quiescent state to avoid constitutive activation and immune pathology.

    2. Simply the right time to turn on insulin

      Francesca M Spagnoli

      Article first published online: 13 MAY 2015 | DOI: 10.15252/embj.201591894

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      Recent work identifies precise induction of NEUROG3 expression in pancreatic progenitor cells as a crucial checkpoint for generating functional human beta cells.

  3. Articles

    1. The stress response neuropeptide CRF increases amyloid-β production by regulating γ-secretase activity

      Hyo-Jin Park, Yong Ran, Joo In Jung, Oliver Holmes, Ashleigh R Price, Lisa Smithson, Carolina Ceballos-Diaz, Chul Han, Michael S Wolfe, Yehia Daaka, Andrey E Ryabinin, Seong-Hun Kim, Richard L Hauger, Todd E Golde and Kevin M Felsenstein

      Article first published online: 11 MAY 2015 | DOI: 10.15252/embj.201488795

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      The critical stress mediator corticotropin releasing factor (CRF) increases amyloid-β production by altering γ-secretase localization and activity, thus providing a link between stress and amyloid-β pathology.

    2. Short loop length and high thermal stability determine genomic instability induced by G-quadruplex-forming minisatellites

      Aurèle Piazza, Michael Adrian, Frédéric Samazan, Brahim Heddi, Florian Hamon, Alexandre Serero, Judith Lopes, Marie-Paule Teulade-Fichou, Anh Tuân Phan and Alain Nicolas

      Article first published online: 8 MAY 2015 | DOI: 10.15252/embj.201490702

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      In vivo formation of G-quadruplex (G4) DNA structures formed by G-rich DNA, which affects various biological processes, remains difficult to predict based on sequence features. A yeast minisatellite instability assay reveals features required for G4 DNA to form replication roadblocks inside cells.

    3. A NAD-dependent glutamate dehydrogenase coordinates metabolism with cell division in Caulobacter crescentus

      François Beaufay, Jérôme Coppine, Aurélie Mayard, Géraldine Laloux, Xavier De Bolle and Régis Hallez

      Article first published online: 7 MAY 2015 | DOI: 10.15252/embj.201490730

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      GdhZ and KidO are complementary negative regulators of FtsZ that connect metabolic conditions to cell division in Caulobacter crescentus. GdhZ is an inhibitor of FtsZ polymerization while KidO prevents FtsZ filament bundling in response to nutrient availability.

    4. Noncanonical regulation of alkylation damage resistance by the OTUD4 deubiquitinase

      Yu Zhao, Mona C Majid, Jennifer M Soll, Joshua R Brickner, Sebastian Dango and Nima Mosammaparast

      Article first published online: 5 MAY 2015 | DOI: 10.15252/embj.201490497

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      Human OTUD4 controls ubiquitination of base-excision repair demethylases ALKBH2 and ALBH3 by coordinating deubiquitinases USP7 and USP9X, while itself acting in a non-catalytic manner.

    5. Adaptation of avian influenza A (H6N1) virus from avian to human receptor-binding preference

      Fei Wang, Jianxun Qi, Yuhai Bi, Wei Zhang, Min Wang, Baorong Zhang, Ming Wang, Jinhua Liu, Jinghua Yan, Yi Shi and George F Gao

      Article first published online: 4 MAY 2015 | DOI: 10.15252/embj.201590960

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      Historical analysis of Influenza H6N1 isolates from 1972 until 2013, when the first human infection occurred, reveals amino acid changes that change receptor binding preference from birds to humans and therefore virus ability to cross the species barrier.

    6. Cerebral nitric oxide represses choroid plexus NFκB-dependent gateway activity for leukocyte trafficking

      Kuti Baruch, Alexander Kertser, Ziv Porat and Michal Schwartz

      Article first published online: 4 MAY 2015 | DOI: 10.15252/embj.201591468

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      Neurodegenerative disorders are associated with excessive nitric oxide (NO) production. New findings show here that NO represses leukocyte trafficking to the CNS via inhibition of the NFκB/p65 signaling pathway.

    7. You have full text access to this OnlineOpen article
      Crystal structures reveal transient PERK luminal domain tetramerization in endoplasmic reticulum stress signaling

      Marta Carrara, Filippo Prischi, Piotr R Nowak and Maruf MU Ali

      Article first published online: 29 APR 2015 | DOI: 10.15252/embj.201489183

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      Structural and functional analyses of the PERK luminal domain reveal a novel tetrameric arrangement, whose transient formation may be an important step in activation of the unfolded protein response.

  4. Reviews

    1. You have full text access to this OnlineOpen article
      Probing disorders of the nervous system using reprogramming approaches

      Justin K Ichida and Evangelos Kiskinis

      Article first published online: 29 APR 2015 | DOI: 10.15252/embj.201591267

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      Kiskinis & Ichida highlight recent progress in neurological disease modeling using iPSCs. The reconstitution of the three-dimensional architecture, including ageing or metabolic parameters will inform the complex nature of neurologic conditions.

  5. Articles

    1. Okazaki fragment maturation involves α-segment error editing by the mammalian FEN1/MutSα functional complex

      Songbai Liu, Guojun Lu, Shafat Ali, Wenpeng Liu, Li Zheng, Huifang Dai, Hongzhi Li, Hong Xu, Yuejin Hua, Yajing Zhou, Janice Ortega, Guo-Min Li, Thomas A Kunkel and Binghui Shen

      Article first published online: 28 APR 2015 | DOI: 10.15252/embj.201489865

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      The key role of proofreading-deficient DNA polymerase α in initiating Okazaki fragment synthesis requires mismatch removal by a dedicated DNA repair process involving mammalian flap endonuclease.

    2. Neuropeptide Y regulates the hematopoietic stem cell microenvironment and prevents nerve injury in the bone marrow

      Min Hee Park, Hee Kyung Jin, Woo-Kie Min, Won Woo Lee, Jeong Eun Lee, Haruhiko Akiyama, Herbert Herzog, Grigori N Enikolopov, Edward H Schuchman and Jae-sung Bae

      Article first published online: 27 APR 2015 | DOI: 10.15252/embj.201490174

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      Neuropeptide Y maintains hematopoietic stem cells in the bone marrow by instructing the stromal microenvironment.

    3. The transcription factor Cabut coordinates energy metabolism and the circadian clock in response to sugar sensing

      Osnat Bartok, Mari Teesalu, Reut Ashwall-Fluss, Varun Pandey, Mor Hanan, Bohdana M Rovenko, Minna Poukkula, Essi Havula, Arieh Moussaieff, Sadanand Vodala, Yaakov Nahmias, Sebastian Kadener and Ville Hietakangas

      Article first published online: 27 APR 2015 | DOI: 10.15252/embj.201591385

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      Sugar feeding in flies induces specific gene expression but also triggers a repressive branch via transcription factor Cabut. Induction of Cabut alters accumulation of the metabolic enzyme PEPCK and provides a regulatory link between nutrient sensing and the circadian clock.

  6. Have you seen?

    1. SHP2: a new target for pro-senescence cancer therapies

      Manuel Serrano

      Article first published online: 27 APR 2015 | DOI: 10.15252/embj.201591616

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      Pharmacological inhibition of the tyrosine phosphatase SHP2 blocks mouse mammary cancer through the induction of senescence.

  7. Editorial

    1. Focus on induced pluripotency and cellular reprogramming

      Thomas Schwarz-Romond, Evangelos Kiskinis and Kevin Eggan

      Article first published online: 27 APR 2015 | DOI: 10.15252/embj.201591615

  8. Have you seen?

    1. Talk among yourselves: RNA sponges mediate cross talk between functionally related messenger RNAs

      Muhammad S Azam and Carin K Vanderpool

      Article first published online: 27 APR 2015 | DOI: 10.15252/embj.201591492

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      Recent work shows that bacterial RNAs can act as sponges for sRNAs, thereby altering the regulatory outcome for downstream target mRNAs.

  9. Resource

    1. You have full text access to this OnlineOpen article
      Discrete domains of gene expression in germinal layers distinguish the development of gyrencephaly

      Camino de Juan Romero, Carl Bruder, Ugo Tomasello, José Miguel Sanz-Anquela and Víctor Borrell

      Article first published online: 27 APR 2015 | DOI: 10.15252/embj.201591176

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      Complex patterns of gene expression emerge in germinal layers during early cortical development of gyrencephalic animals. These modular expression patterns map the eventual location of folds and fissures.

  10. Articles

    1. You have full text access to this OnlineOpen article
      Sox2, Tlx, Gli3, and Her9 converge on Rx2 to define retinal stem cells in vivo

      Robert Reinhardt, Lázaro Centanin, Tinatini Tavhelidse, Daigo Inoue, Beate Wittbrodt, Jean-Paul Concordet, Juan Ramón Martinez-Morales and Joachim Wittbrodt

      Article first published online: 23 APR 2015 | DOI: 10.15252/embj.201490706

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      This study establishes Rx2 as functional determinant of neuro-epithelial progenitor fate and uncovers the gene regulatory network that governs Rx2 expression.

  11. Reviews

    1. Forward engineering neuronal diversity using direct reprogramming

      Rachel K Tsunemoto, Kevin T Eade, Joel W Blanchard and Kristin K Baldwin

      Article first published online: 23 APR 2015 | DOI: 10.15252/embj.201591402

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      Kristin Baldwin & colleagues outline most recent routes to generate a huge spectrum of neuronal subtypes in vitro. Their functionality and resemblance of endogenous tissue raises hopes for cell replacement therapies.

  12. Articles

    1. Controlled induction of human pancreatic progenitors produces functional beta-like cells in vitro

      Holger A Russ, Audrey V Parent, Jennifer J Ringler, Thomas G Hennings, Gopika G Nair, Mayya Shveygert, Tingxia Guo, Sapna Puri, Leena Haataja, Vincenzo Cirulli, Robert Blelloch, Greg L Szot, Peter Arvan and Matthias Hebrok

      Article first published online: 23 APR 2015 | DOI: 10.15252/embj.201591058

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      Focusing on developmental mechanisms, the results of this study further accelerate successful differentiation of human ESCs into functional pancreatic beta cells.

    2. You have full text access to this OnlineOpen article
      Synthetic viability genomic screening defines Sae2 function in DNA repair

      Fabio Puddu, Tobias Oelschlaegel, Ilaria Guerini, Nicola J Geisler, Hengyao Niu, Mareike Herzog, Israel Salguero, Bernardo Ochoa-Montaño, Emmanuelle Viré, Patrick Sung, David J Adams, Thomas M Keane and Stephen P Jackson

      Article first published online: 21 APR 2015 | DOI: 10.15252/embj.201590973

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      Identification of Mre11 mutations suppressing the DNA damage sensitivity of Sae2 mutant cells reveals how these resection nucleases cooperate in mitotic yeast cells.

  13. Have you seen?

    1. RNA degradation drives stem cell differentiation

      Chih-Hong Lou, Eleen Y Shum and Miles F Wilkinson

      Article first published online: 21 APR 2015 | DOI: 10.15252/embj.201591631

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      The nonsense-mediated decay pathway contributes to stem cell differentiation by reducing mRNA levels for key pluripotency genes.

  14. Articles

    1. Dampening DNA damage checkpoint signalling via coordinated BRCT domain interactions

      José R Cussiol, Carolyn M Jablonowski, Askar Yimit, Grant W Brown and Marcus B Smolka

      Article first published online: 20 APR 2015 | DOI: 10.15252/embj.201490834

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      The DNA repair scaffold proteins Slx4 and Rtt107 utilize a minimal multi-BRCT-domain module for phosphatase-independent down-regulation of DNA damage response signals in yeast.

  15. Have you seen

    1. REV7/MAD2L2: the multitasking maestro emerges as a barrier to recombination

      Julian E Sale

      Article first published online: 20 APR 2015 | DOI: 10.15252/embj.201591697

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      Two new papers implicating REV7/MAD2L2 in DNA double strand break repair pathway choice further extend the impressive functional spectrum of this translesion synthesis and mitotic control factor.

  16. Articles

    1. Repression of SRF target genes is critical for Myc-dependent apoptosis of epithelial cells

      Katrin E Wiese, Heidi M Haikala, Björn von Eyss, Elmar Wolf, Cyril Esnault, Andreas Rosenwald, Richard Treisman, Juha Klefström and Martin Eilers

      Article first published online: 20 APR 2015 | DOI: 10.15252/embj.201490467

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      Oncogenic levels of Myc promote apoptosis by repressing cell adhesion molecules and Akt signaling in epithelial cells, counteracting serum-response factor activity.

    2. USP18 lack in microglia causes destructive interferonopathy of the mouse brain

      Tobias Goldmann, Nicolas Zeller, Jenni Raasch, Katrin Kierdorf, Kathrin Frenzel, Lars Ketscher, Anja Basters, Ori Staszewski, Stefanie M Brendecke, Alena Spiess, Tuan Leng Tay, Clemens Kreutz, Jens Timmer, Grazia MS Mancini, Thomas Blank, Günter Fritz, Knut Biber, Roland Lang, Danielle Malo, Doron Merkler, Mathias Heikenwälder, Klaus-Peter Knobeloch and Marco Prinz

      Article first published online: 20 APR 2015 | DOI: 10.15252/embj.201490791

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      The non-catalytic anti-inflammatory function of a deubiquitination enzyme plays a key role in preventing microglia activation and neuroinflammation in mouse brains.

    3. The first murine zygotic transcription is promiscuous and uncoupled from splicing and 3′ processing

      Ken-ichiro Abe, Ryoma Yamamoto, Vedran Franke, Minjun Cao, Yutaka Suzuki, Masataka G Suzuki, Kristian Vlahovicek, Petr Svoboda, Richard M Schultz and Fugaku Aoki

      Article first published online: 20 APR 2015 | DOI: 10.15252/embj.201490648

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      Transcriptome analysis in mouse 1-cell embryos reveals widespread transcription of intergenic regions devoid of core-promoter elements. The resulting RNAs, possibly involved in chromatin remodeling, are poorly processed to prevent aberrant expression.

    4. You have full text access to this OnlineOpen article
      Expression of Ca2+-permeable two-pore channels rescues NAADP signalling in TPC-deficient cells

      Margarida Ruas, Lianne C Davis, Cheng-Chang Chen, Anthony J Morgan, Kai-Ting Chuang, Timothy F Walseth, Christian Grimm, Clive Garnham, Trevor Powell, Nick Platt, Frances M Platt, Martin Biel, Christian Wahl-Schott, John Parrington and Antony Galione

      Article first published online: 14 APR 2015 | DOI: 10.15252/embj.201490009

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      By presenting a new double-knockout mouse model this study demonstrates that two-pore channels (TPCs) are responsible for NAADP-dependent Ca2+ release from endo-lysosomes.

  17. Have you seen?

    1. A grab to move on: ER–endosome contacts in membrane protrusion formation and neurite outgrowth

      Michael Krauß and Volker Haucke

      Article first published online: 10 APR 2015 | DOI: 10.15252/embj.201591553

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      ER-localized protrudin and phosphatidylinositol 3-phosphate and Rab7 GTPase on late endosomes establish contact sites, to transfer kinesin-1 to the motor adaptor FYCO1, allowing for the movement of late endosomes and thus outgrowth of protrusions and neurites.

  18. Articles

    1. You have full text access to this OnlineOpen article
      Smg6/Est1 licenses embryonic stem cell differentiation via nonsense-mediated mRNA decay

      Tangliang Li, Yue Shi, Pei Wang, Luis Miguel Guachalla, Baofa Sun, Tjard Joerss, Yu-Sheng Chen, Marco Groth, Anja Krueger, Matthias Platzer, Yun-Gui Yang, Karl Lenhard Rudolph and Zhao-Qi Wang

      Article first published online: 14 MAR 2015 | DOI: 10.15252/embj.201489947

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      New genetic data show that the NMD pathway is dispensable for growth of embryonic stem cells (ESCs) but essential for differentiation and reprogramming via repression of key pluripotency genes.

    2. Shp2 signaling suppresses senescence in PyMT-induced mammary gland cancer in mice

      Linxiang Lan, Jane D Holland, Jingjing Qi, Stefanie Grosskopf, Regina Vogel, Balázs Györffy, Annika Wulf-Goldenberg and Walter Birchmeier

      Article first published online: 3 MAR 2015 | DOI: 10.15252/embj.201489004

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      Tyrosine phosphatase Shp2, upregulated in human breast cancer, regulates Src, FAK, and MAPK signaling pathway to suppress senescence and promote tumorigenesis in mouse models.

    3. You have full text access to this OnlineOpen article
      Cross talk between ABC transporter mRNAs via a target mRNA-derived sponge of the GcvB small RNA

      Masatoshi Miyakoshi, Yanjie Chao and Jörg Vogel

      Article first published online: 28 JAN 2015 | DOI: 10.15252/embj.201490546

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      Decay of the bacterial GcvB sRNA, which keeps it from regulating its mRNA targets, is triggered by a 3′-UTR-derived fragment from a target mRNA. This ability of mRNAs to compete for regulatory RNA interaction presents a new mode of RNA cross talk in bacteria.

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