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  • Progranulin and TMEM106B: when two become wan
    EMBO Rep. (IF 7.497) Pub Date : 2020-09-28
    Emma L Clayton; Adrian M Isaacs

    Mutations in GRN, which encodes progranulin, are a common cause of familial frontotemporal dementia (FTD). FTD is a devastating disease characterised by neuronal loss in the frontal and temporal lobes that leads to changes in personality, behaviour and language. There are no effective treatments for this complex condition. TMEM106B is a well‐recognised risk factor for FTD caused by GRN mutation. While

  • Iron loss triggers mitophagy through induction of mitochondrial ferritin
    EMBO Rep. (IF 7.497) Pub Date : 2020-09-25
    Yuichi Hara; Izumi Yanatori; Atsushi Tanaka; Fumio Kishi; John J Lemasters; Sohji Nishina; Kyo Sasaki; Keisuke Hino

    Mitochondrial quality is controlled by the selective removal of damaged mitochondria through mitophagy. Mitophagy impairment is associated with aging and many pathological conditions. An iron loss induced by iron chelator triggers mitophagy by a yet unknown mechanism. This type of mitophagy may have therapeutic potential, since iron chelators are clinically used. Here, we aimed to clarify the mechanisms

  • Regulation of neuronal commitment in mouse embryonic stem cells by the Reno1/Bahcc1 locus.
    EMBO Rep. (IF 7.497) Pub Date : 2020-09-24
    Hadas Hezroni,Rotem Ben-Tov Perry,Noa Gil,Neta Degani,Igor Ulitsky

    Mammalian genomes encode thousands of long noncoding RNAs (lncRNAs), yet the biological functions of most of them remain unknown. A particularly rich repertoire of lncRNAs found in mammalian brain and in the early embryo. We used RNA‐seq and computational analysis to prioritize lncRNAs that may regulate commitment of pluripotent cells to a neuronal fate and perturbed their expression prior to neuronal

  • Protease protection assays show polypeptide movement into the SecY channel by power strokes of the SecA ATPase.
    EMBO Rep. (IF 7.497) Pub Date : 2020-09-24
    Marco A Catipovic,Tom A Rapoport

    Bacterial secretory proteins are translocated post‐translationally by the SecA ATPase through the protein‐conducting SecY channel in the plasma membrane. During the ATP hydrolysis cycle, SecA undergoes large conformational changes of its two‐helix finger and clamp domains, but how these changes result in polypeptide movement is unclear. Here, we use a reconstituted purified system and protease protection

  • Nutrient metabolism and cancer in the in vivo context: a metabolic game of give and take.
    EMBO Rep. (IF 7.497) Pub Date : 2020-09-23
    Patricia Altea-Manzano,Alejandro M Cuadros,Lindsay A Broadfield,Sarah-Maria Fendt

    Nutrients are indispensable resources that provide the macromolecular building blocks and energy requirements for sustaining cell growth and survival. Cancer cells require several key nutrients to fulfill their changing metabolic needs as they progress through stages of development. Moreover, both cell‐intrinsic and microenvironment‐influenced factors determine nutrient dependencies throughout cancer

  • Postmitotic expansion of cell nuclei requires nuclear actin filament bundling by α-actinin 4.
    EMBO Rep. (IF 7.497) Pub Date : 2020-09-22
    Sylvia Krippner,Jannik Winkelmeier,Julian Knerr,Dominique T Brandt,David Virant,Carsten Schwan,Ulrike Endesfelder,Robert Grosse

    The actin cytoskeleton operates in a multitude of cellular processes including cell shape and migration, mechanoregulation, and membrane or organelle dynamics. However, its filamentous properties and functions inside the mammalian cell nucleus are less well explored. We previously described transient actin assembly at mitotic exit that promotes nuclear expansion during chromatin decondensation. Here

  • A regulatory region on RIPK2 is required for XIAP binding and NOD signaling activity.
    EMBO Rep. (IF 7.497) Pub Date : 2020-09-21
    Valentin J Heim,Laura F Dagley,Che A Stafford,Fynn M Hansen,Elise Clayer,Aleksandra Bankovacki,Andrew I Webb,Isabelle S Lucet,John Silke,Ueli Nachbur

    Signaling via the intracellular pathogen receptors nucleotide‐binding oligomerization domain‐containing proteins NOD1 and NOD2 requires receptor interacting kinase 2 (RIPK2), an adaptor kinase that can be targeted for the treatment of various inflammatory diseases. However, the molecular mechanisms of how RIPK2 contributes to NOD signaling are not completely understood. We generated FLAG‐tagged RIPK2

  • In memoriam Paolo Sassone-Corsi (1956-2020).
    EMBO Rep. (IF 7.497) Pub Date : 2020-09-21
    Angela Giangrande,Pierre Chambon

  • Enzymatic degradation of RNA causes widespread protein aggregation in cell and tissue lysates.
    EMBO Rep. (IF 7.497) Pub Date : 2020-09-18
    Johan Aarum,Claudia P Cabrera,Tania A Jones,Shiron Rajendran,Rocco Adiutori,Gavin Giovannoni,Michael R Barnes,Andrea Malaspina,Denise Sheer

    Most proteins in cell and tissue lysates are soluble. We show here that in lysate from human neurons, more than 1,300 proteins are maintained in a soluble and functional state by association with endogenous RNA, as degradation of RNA invariably leads to protein aggregation. The majority of these proteins lack conventional RNA‐binding domains. Using synthetic oligonucleotides, we identify the importance

  • G-Quadruplexes act as sequence-dependent protein chaperones.
    EMBO Rep. (IF 7.497) Pub Date : 2020-09-18
    Adam Begeman,Ahyun Son,Theodore J Litberg,Tadeusz H Wroblewski,Thane Gehring,Veronica Huizar Cabral,Jennifer Bourne,Zhenyu Xuan,Scott Horowitz

    Maintaining proteome health is important for cell survival. Nucleic acids possess the ability to prevent protein aggregation more efficiently than traditional chaperone proteins. In this study, we explore the sequence specificity of the chaperone activity of nucleic acids. Evaluating over 500 nucleic acid sequences’ effects on protein aggregation, we show that the holdase chaperone effect of nucleic

  • TET2 promotes anti-tumor immunity by governing G-MDSCs and CD8+ T-cell numbers.
    EMBO Rep. (IF 7.497) Pub Date : 2020-09-14
    Shuangqi Li,Jiuxing Feng,Feizhen Wu,Jiabin Cai,Xinyu Zhang,Haikun Wang,Irfete S Fetahu,Isabella Iwanicki,Dingailu Ma,Tao Hu,Hang Liu,Bingjie Wang,Guoming Shi,Li Tan,Yujiang Geno Shi

    The host immune response is a fundamental mechanism for attenuating cancer progression. Here we report a role for the DNA demethylase and tumor suppressor TET2 in host anti‐tumor immunity. Deletion of Tet2 in mice elevates IL‐6 levels upon tumor challenge. Elevated IL‐6 stimulates immunosuppressive granulocytic myeloid‐derived suppressor cells (G‐MDSCs), which in turn reduce CD8+ T cells upon tumor

  • Loss of TMEM106B potentiates lysosomal and FTLD-like pathology in progranulin-deficient mice.
    EMBO Rep. (IF 7.497) Pub Date : 2020-09-14
    Georg Werner,Markus Damme,Martin Schludi,Johannes Gnörich,Karin Wind,Katrin Fellerer,Benedikt Wefers,Wolfgang Wurst,Dieter Edbauer,Matthias Brendel,Christian Haass,Anja Capell

    Single nucleotide polymorphisms (SNPs) in TMEM106B encoding the lysosomal type II transmembrane protein 106B increase the risk for frontotemporal lobar degeneration (FTLD) of GRN (progranulin gene) mutation carriers. Currently, it is unclear if progranulin (PGRN) and TMEM106B are synergistically linked and if a gain or a loss of function of TMEM106B is responsible for the increased disease risk of

  • Exploring GPCR-arrestin interfaces with genetically encoded crosslinkers.
    EMBO Rep. (IF 7.497) Pub Date : 2020-09-14
    Thore Böttke,Stefan Ernicke,Robert Serfling,Christian Ihling,Edyta Burda,Vsevolod V Gurevich,Andrea Sinz,Irene Coin

    β‐arrestins (βarr1 and βarr2) are ubiquitous regulators of G protein‐coupled receptor (GPCR) signaling. Available data suggest that β‐arrestins dock to different receptors in different ways. However, the structural characterization of GPCR‐arrestin complexes is challenging and alternative approaches to study GPCR‐arrestin complexes are needed. Here, starting from the finger loop as a major site for

  • A malectin-like receptor kinase regulates cell death and pattern-triggered immunity in soybean.
    EMBO Rep. (IF 7.497) Pub Date : 2020-09-14
    Dongmei Wang,Xiangxiu Liang,Yazhou Bao,Suxin Yang,Xiong Zhang,Hui Yu,Qian Zhang,Guangyuan Xu,Xianzhong Feng,Daolong Dou

    Plant cells can sense conserved molecular patterns through pattern recognition receptors (PRRs) and initiate pattern‐triggered immunity (PTI). Details of the PTI signaling network are starting to be uncovered in Arabidopsis, but are still poorly understood in other species, including soybean (Glycine max). In this study, we perform a forward genetic screen for autoimmunity‐related lesion mimic mutants

  • PEBP1 suppresses HIV transcription and induces latency by inactivating MAPK/NF-κB signaling.
    EMBO Rep. (IF 7.497) Pub Date : 2020-09-14
    Xinyi Yang,Yanan Wang,Panpan Lu,Yinzhong Shen,Xiaying Zhao,Yuqi Zhu,Zhengtao Jiang,He Yang,Hanyu Pan,Lin Zhao,Yangcheng Zhong,Jing Wang,Zhiming Liang,Xiaoting Shen,Daru Lu,Shibo Jiang,Jianqing Xu,Hao Wu,Hongzhou Lu,Guochun Jiang,Huanzhang Zhu

    The latent HIV‐1 reservoir is a major barrier to viral eradication. However, our understanding of how HIV‐1 establishes latency is incomplete. Here, by performing a genome‐wide CRISPR‐Cas9 knockout library screen, we identify phosphatidylethanolamine‐binding protein 1 (PEBP1), also known as Raf kinase inhibitor protein (RKIP), as a novel gene inducing HIV latency. Depletion of PEBP1 leads to the reactivation

  • Response by the author.
    EMBO Rep. (IF 7.497) Pub Date : 2020-09-14
    Gian Paolo Dotto

  • On physics and biology.
    EMBO Rep. (IF 7.497) Pub Date : 2020-09-14
    Min-Liang Wong

  • Do you miss the conference circuit? I surely don't.
    EMBO Rep. (IF 7.497) Pub Date : 2020-09-11
    David R Smith

  • The actin modulator hMENA regulates GAS6-AXL axis and pro-tumor cancer/stromal cell cooperation.
    EMBO Rep. (IF 7.497) Pub Date : 2020-09-10
    Roberta Melchionna,Sheila Spada,Francesca Di Modugno,Daniel D'Andrea,Anna Di Carlo,Mariangela Panetta,Anna Maria Mileo,Isabella Sperduti,Barbara Antoniani,Enzo Gallo,Rita T Lawlor,Lorenzo Piemonti,Paolo Visca,Michele Milella,Gian Luca Grazi,Francesco Facciolo,Emily Chen,Aldo Scarpa,Paola Nisticò

    The dynamic interplay between cancer cells and cancer‐associated fibroblasts (CAFs) is regulated by multiple signaling pathways, which can lead to cancer progression and therapy resistance. We have previously demonstrated that hMENA, a member of the actin regulatory protein of Ena/VASP family, and its tissue‐specific isoforms influence a number of intracellular signaling pathways related to cancer

  • Mitochondrial respiration is required to provide amino acids during fermentative proliferation of fission yeast.
    EMBO Rep. (IF 7.497) Pub Date : 2020-09-07
    Michal Malecki,Stephan Kamrad,Markus Ralser,Jürg Bähler

    When glucose is available, many organisms repress mitochondrial respiration in favour of aerobic glycolysis, or fermentation in yeast, that suffices for ATP production. Fission yeast cells, however, rely partially on respiration for rapid proliferation under fermentative conditions. Here, we determined the limiting factors that require respiratory function during fermentation. When inhibiting the electron

  • Cell cycle dynamics of lamina-associated DNA.
    EMBO Rep. (IF 7.497) Pub Date : 2020-09-07
    Tom van Schaik,Mabel Vos,Daan Peric-Hupkes,Patrick Hn Celie,Bas van Steensel

    In mammalian interphase nuclei, more than one thousand large genomic regions are positioned at the nuclear lamina (NL). These lamina‐associated domains (LADs) are involved in gene regulation and may provide a backbone for the folding of interphase chromosomes. Little is known about the dynamics of LADs during interphase, in particular at the onset of G1 phase and during DNA replication. We developed

  • Open Access, Plan S, and researchers' needs.
    EMBO Rep. (IF 7.497) Pub Date : 2020-09-07
    Shina Caroline Lynn Kamerlin

    Mandates with the aim to enforce Open Access publishing, such as Plan S, need to respect researchers' needs and should contribute to the broader goal of Open Science.

  • The prospects of Excellence Initiatives in research: Key Ingredients for a Successful Academic Research Institute.
    EMBO Rep. (IF 7.497) Pub Date : 2020-09-07
    Wolf B Frommer,Kenichiro Itami

    Many ingredients need to come together for a new research institute to become successful. What is often overlooked though is a long-term financial perspective.

  • Keys to the Kingdom: GPCR phosphorylation patterns direct β-arrestin.
    EMBO Rep. (IF 7.497) Pub Date : 2020-08-24
    Richard T Premont

    The β‐arrestin proteins are key regulators of G protein‐coupled receptors, serving at least three distinct functions: inhibiting receptor signaling through G proteins, directing receptor trafficking from the cell surface after activation, and transmitting receptor‐initiated signals directly. How the two β‐arrestin proteins perform these many functions for hundreds of receptor types throughout the body

  • LRP6 lets Merlin go in times of nutrient scarcity.
    EMBO Rep. (IF 7.497) Pub Date : 2020-08-20
    Kenneth Kin Lam Wong,Esther M Verheyen

    Cells take advantage of cross‐talk in signaling pathways to integrate diverse signals and produce coordinated responses. In this issue of EMBO Reports, Jeong et al discover that the Wnt co‐receptor, low‐density lipoprotein (LDL) receptor‐related protein LRP6, negatively regulates Hippo signaling by serving as a binding sink to sequester and inhibit Merlin, an activator of Hippo signaling (Jeong et al

  • So close, no matter how far: multiple paths connecting transcription to mRNA translation in eukaryotes.
    EMBO Rep. (IF 7.497) Pub Date : 2020-08-16
    Boris Slobodin,Rivka Dikstein

    Transcription of DNA into mRNA and translation of mRNA into proteins are two major processes underlying gene expression. Due to the distinct molecular mechanisms, timings, and locales of action, these processes are mainly considered to be independent. During the last two decades, however, multiple factors and elements were shown to coordinate transcription and translation, suggesting an intricate level

  • Transient Dux expression facilitates nuclear transfer and induced pluripotent stem cell reprogramming.
    EMBO Rep. (IF 7.497) Pub Date : 2020-07-27
    Lei Yang,Xuefei Liu,Lishuang Song,Anqi Di,Guanghua Su,Chunling Bai,Zhuying Wei,Guangpeng Li

    Cloned animals generated by somatic cell nuclear transfer (SCNT) have been reported for many years; however, SCNT is extremely inefficient, and zygotic genome activation (ZGA) is required for SCNT‐mediated somatic cell reprogramming. To identify candidate factors that facilitate ZGA in SCNT‐mediated reprogramming, we performed siRNA‐repressor and mRNA‐inducer screenings, which reveal Dux, Dppa2, and

  • The regulation of glucose and lipid homeostasis via PLTP as a mediator of BAT-liver communication.
    EMBO Rep. (IF 7.497) Pub Date : 2020-07-16
    Carlos H Sponton,Takashi Hosono,Junki Taura,Mark P Jedrychowski,Takeshi Yoneshiro,Qiang Wang,Makoto Takahashi,Yumi Matsui,Kenji Ikeda,Yasuo Oguri,Kazuki Tajima,Kosaku Shinoda,Rachana N Pradhan,Yong Chen,Zachary Brown,Lindsay S Roberts,Carl C Ward,Hiroki Taoka,Yoko Yokoyama,Mitsuhiro Watanabe,Hiroshi Karasawa,Daniel K Nomura,Shingo Kajimura

    While brown adipose tissue (BAT) is well‐recognized for its ability to dissipate energy in the form of heat, recent studies suggest multifaced roles of BAT in the regulation of glucose and lipid homeostasis beyond stimulating thermogenesis. One of the functions involves interorgan communication with metabolic organs, such as the liver, through BAT‐derived secretory factors, a.k.a., batokine. However

  • Key phosphorylation sites in GPCRs orchestrate the contribution of β-Arrestin 1 in ERK1/2 activation.
    EMBO Rep. (IF 7.497) Pub Date : 2020-07-26
    Mithu Baidya,Punita Kumari,Hemlata Dwivedi-Agnihotri,Shubhi Pandey,Madhu Chaturvedi,Tomasz Maciej Stepniewski,Kouki Kawakami,Yubo Cao,Stéphane A Laporte,Jana Selent,Asuka Inoue,Arun K Shukla

    β‐arrestins (βarrs) are key regulators of G protein‐coupled receptor (GPCR) signaling and trafficking, and their knockdown typically leads to a decrease in agonist‐induced ERK1/2 MAP kinase activation. Interestingly, for some GPCRs, knockdown of βarr1 augments agonist‐induced ERK1/2 phosphorylation although a mechanistic basis for this intriguing phenomenon is unclear. Here, we use selected GPCRs to

  • LDL receptor-related protein LRP6 senses nutrient levels and regulates Hippo signaling.
    EMBO Rep. (IF 7.497) Pub Date : 2020-08-07
    Wonyoung Jeong,Soyoung Kim,Ukjin Lee,Zhendong A Zhong,Mikhail Savitsky,Hyeryun Kwon,Jiyoung Kim,Taebok Lee,Jin Won Cho,Bart O Williams,Vladimir L Katanaev,Eek-Hoon Jho

    Controlled cell growth and proliferation are essential for tissue homeostasis and development. Wnt and Hippo signaling are well known as positive and negative regulators of cell proliferation, respectively. The regulation of Hippo signaling by the Wnt pathway has been shown, but how and which components of Wnt signaling are involved in the activation of Hippo signaling during nutrient starvation are

  • The breast cancer oncogene IKKε coordinates mitochondrial function and serine metabolism.
    EMBO Rep. (IF 7.497) Pub Date : 2020-08-11
    Ruoyan Xu,William Jones,Ewa Wilcz-Villega,Ana Sh Costa,Vinothini Rajeeve,Robert B Bentham,Kevin Bryson,Ai Nagano,Busra Yaman,Sheila Olendo Barasa,Yewei Wang,Claude Chelala,Pedro Cutillas,Gyorgy Szabadkai,Christian Frezza,Katiuscia Bianchi

    IκB kinase ε (IKKε) is a key molecule at the crossroads of inflammation and cancer. Known to regulate cytokine secretion via NFκB and IRF3, the kinase is also a breast cancer oncogene, overexpressed in a variety of tumours. However, to what extent IKKε remodels cellular metabolism is currently unknown. Here, we used metabolic tracer analysis to show that IKKε orchestrates a complex metabolic reprogramming

  • The microRNA/TET3/REST axis is required for olfactory globose basal cell proliferation and male behavior.
    EMBO Rep. (IF 7.497) Pub Date : 2020-07-17
    Dong Yang,Xiangbo Wu,Yanfen Zhou,Weina Wang,Zhenshan Wang

    In the main olfactory epithelium (MOE), new olfactory sensory neurons (OSNs) are persistently generated to replace lost neurons throughout an organism's lifespan. This process predominantly depends on the proliferation of globose basal cells (GBCs), the actively dividing stem cells in the MOE. Here, by using CRISPR/Cas9 and RNAi coupled with adeno‐associated virus (AAV) nose delivery approaches, we

  • Mitophagy regulates integrity of mitochondria at synapses and is critical for synaptic maintenance.
    EMBO Rep. (IF 7.497) Pub Date : 2020-07-06
    Sinsuk Han,Yu Young Jeong,Preethi Sheshadri,Xiao Su,Qian Cai

    Synaptic mitochondria are particularly vulnerable to physiological insults, and defects in synaptic mitochondria are linked to early pathophysiology of Alzheimer's disease (AD). Mitophagy, a cargo‐specific autophagy for elimination of dysfunctional mitochondria, constitutes a key quality control mechanism. However, how mitophagy ensures synaptic mitochondrial integrity remains largely unknown. Here

  • Hypothalamic CDK4 regulates thermogenesis by modulating sympathetic innervation of adipose tissues.
    EMBO Rep. (IF 7.497) Pub Date : 2020-07-12
    Judit Castillo-Armengol,Valentin Barquissau,Sarah Geller,Honglei Ji,Ilenia Severi,Wiebe Venema,Eric Aria Fenandez,Catherine Moret,Katharina Huber,Lucia C Leal-Esteban,Anita Nasrallah,Laia Martinez-Carreres,Guy Niederhäuser,Patricia Seoane-Collazo,Sylviane Lagarrigue,Miguel López,Antonio Giordano,Sophie Croizier,Bernard Thorens,Isabel C Lopez-Mejia,Lluis Fajas

    This study investigated the role of CDK4 in the oxidative metabolism of brown adipose tissue (BAT). BAT from Cdk4−/− mice exhibited fewer lipids and increased mitochondrial volume and expression of canonical thermogenic genes, rendering these mice more resistant to cold exposure. Interestingly, these effects were not BAT cell‐autonomous but rather driven by increased sympathetic innervation. In particular

  • Aster-C coordinates with COP I vesicles to regulate lysosomal trafficking and activation of mTORC1.
    EMBO Rep. (IF 7.497) Pub Date : 2020-07-09
    Jun Zhang,John-Paul Andersen,Haoran Sun,Xuyun Liu,Nahum Sonenberg,Jia Nie,Yuguang Shi

    Nutrient sensing by the mTOR complex 1 (mTORC1) requires its translocation to the lysosomal membrane. Upon amino acids removal, mTORC1 becomes cytosolic and inactive, yet its precise subcellular localization and the mechanism of inhibition remain elusive. Here, we identified Aster‐C as a negative regulator of mTORC1 signaling. Aster‐C earmarked a special rough ER subdomain where it sequestered mTOR

  • PAX6D instructs neural retinal specification from human embryonic stem cell-derived neuroectoderm.
    EMBO Rep. (IF 7.497) Pub Date : 2020-07-23
    Yunlong Tao,Jingyuan Cao,Mingxing Li,Brianna Hoffmann,Ke Xu,Jing Chen,Xin Lu,Fangliang Guo,Xiang Li,M Joseph Phillips,David M Gamm,Hong Chen,Su-Chun Zhang

    PAX6 is essential for neural retina (NR) and forebrain development but how PAX6 instructs NR versus forebrain specification remains unknown. We found that the paired‐less PAX6, PAX6D, is expressed in NR cells during human eye development and along human embryonic stem cell (hESC) specification to retinal cells. hESCs deficient for PAX6D failed to enter NR specification. Induced expression of PAX6D

  • Autoimmunity gene IRGM suppresses cGAS-STING and RIG-I-MAVS signaling to control interferon response.
    EMBO Rep. (IF 7.497) Pub Date : 2020-07-27
    Kautilya Kumar Jena,Subhash Mehto,Parej Nath,Nishant Ranjan Chauhan,Rinku Sahu,Kollori Dhar,Saroj Kumar Das,Srinivasa Prasad Kolapalli,Krushna C Murmu,Ashish Jain,Sivaram Krishna,Bhabani Sankar Sahoo,Soma Chattopadhyay,Tor Erik Rusten,Punit Prasad,Swati Chauhan,Santosh Chauhan

    Activation of the type 1 interferon response is extensively connected to the pathogenesis of autoimmune diseases. Loss of function of Immunity Related GTPase M (IRGM) has also been associated to several autoimmune diseases, but its mechanism of action is unknown. Here, we found that IRGM is a master negative regulator of the interferon response. Several nucleic acid‐sensing pathways leading to interferon‐stimulated

  • Extended synaptotagmin regulates membrane contact site structure and lipid transfer function in vivo.
    EMBO Rep. (IF 7.497) Pub Date : 2020-07-27
    Vaisaly R Nath,Shirish Mishra,Bishal Basak,Deepti Trivedi,Padinjat Raghu

    Inter‐organelle communication between closely apposed membranes is proposed at membrane contact sites (MCS). However, the regulation of MCS structure and their functional relevance in vivo remain debated. The extended synaptotagmins (Esyt) are evolutionarily conserved proteins proposed to function at MCS. However, loss of all three Esyts in yeast or mammals shows minimal phenotypes questioning the

  • The deubiquitinase USP44 promotes Treg function during inflammation by preventing FOXP3 degradation.
    EMBO Rep. (IF 7.497) Pub Date : 2020-07-09
    Jing Yang,Ping Wei,Joseph Barbi,Qianru Huang,Evan Yang,Yakun Bai,Jia Nie,Yanhang Gao,Jinhui Tao,Ying Lu,Chichu Xie,Xiaoxia Hou,Jiazi Ren,Xingmei Wu,Jian Meng,Ying Zhang,Juan Fu,Wei Kou,Yayi Gao,Zuojia Chen,Rui Liang,Andy Tsun,Dan Li,Wenzhi Guo,Shuijun Zhang,Song-Guo Zheng,Junqi Niu,Paul Galardy,Xuemei Tong,Guochao Shi,Huabin Li,Fan Pan,Bin Li

    The transcription factor forkhead box P3 (FOXP3) is essential for the development of regulatory T cells (Tregs) and their function in immune homeostasis. Previous studies have shown that in natural Tregs (nTregs), FOXP3 can be regulated by polyubiquitination and deubiquitination. However, the molecular players active in this pathway, especially those modulating FOXP3 by deubiquitination in the distinct

  • Amyloid aggregates accumulate in melanoma metastasis modulating YAP activity.
    EMBO Rep. (IF 7.497) Pub Date : 2020-08-04
    Vittoria Matafora,Francesco Farris,Umberto Restuccia,Simone Tamburri,Giuseppe Martano,Clara Bernardelli,Andrea Sofia,Federica Pisati,Francesca Casagrande,Luca Lazzari,Silvia Marsoni,Emanuela Bonoldi,Angela Bachi

    Melanoma progression is generally associated with increased transcriptional activity mediated by the Yes‐associated protein (YAP). Mechanical signals from the extracellular matrix are sensed by YAP, which then activates the expression of proliferative genes, promoting melanoma progression and drug resistance. Which extracellular signals induce mechanotransduction, and how this is mediated, is not completely

  • HDAC inhibitors tune miRNAs in extracellular vesicles of dystrophic muscle-resident mesenchymal cells.
    EMBO Rep. (IF 7.497) Pub Date : 2020-08-05
    Martina Sandonà,Silvia Consalvi,Luca Tucciarone,Marco De Bardi,Manuel Scimeca,Daniela Francesca Angelini,Valentina Buffa,Adele D'Amico,Enrico Silvio Bertini,Sara Cazzaniga,Paolo Bettica,Marina Bouché,Antonella Bongiovanni,Pier Lorenzo Puri,Valentina Saccone

    We show that extracellular vesicles (EVs) released by mesenchymal cells (i.e., fibro–adipogenic progenitors—FAPs) mediate microRNA (miR) transfer to muscle stem cells (MuSCs) and that exposure of dystrophic FAPs to HDAC inhibitors (HDACis) increases the intra‐EV levels of a subset of miRs, which cooperatively target biological processes of therapeutic interest, including regeneration, fibrosis, and

  • CSAG2 is a cancer-specific activator of SIRT1.
    EMBO Rep. (IF 7.497) Pub Date : 2020-08-05
    Xu Yang,Patrick Ryan Potts

    SIRT1 is a NAD+‐dependent deacetylase that controls key metabolic and signaling pathways, including inactivating the p53 tumor suppressor. However, the mechanisms controlling SIRT1 enzymatic activity in the context of cancer are unclear. Here, we show that the previously undescribed CSAG2 protein is a direct activator of SIRT1. CSAG2 is normally restricted to expression in the male germline but is

  • Public Health struggles to square hygiene with diversity: Research on the link between microbiomes and immune function puts the "hygiene hypothesis" to rest.
    EMBO Rep. (IF 7.497) Pub Date : 2020-09-03
    Philip Hunter

    The 'Hygiene Hypothesis' to explain the rise in allergies is being replaced by a more nuanced picture of how the immune system interacts with environmental microbes.

  • Autotaxin loss accelerates intestinal inflammation by suppressing TLR4-mediated immune responses.
    EMBO Rep. (IF 7.497) Pub Date : 2020-09-01
    Su Jin Kim,Cody Howe,Jonathon Mitchell,Jieun Choo,Alexandra Powers,Angelos Oikonomopoulos,Charalabos Pothoulakis,Daniel W Hommes,Eunok Im,Sang Hoon Rhee

    Autotaxin (ATX) converts lysophosphatidylcholine and sphingosyl‐phosphorylcholine into lysophosphatidic acid and sphingosine 1‐phosphate, respectively. Despite the pivotal function of ATX in lipid metabolism, mechanisms by which ATX regulates immune and inflammatory disorders remain elusive. Here, using myeloid cell lineage‐restricted Atx knockout mice, we show that Atx deficiency disrupts membrane

  • The second coming: The comeback of the live vaccines.
    EMBO Rep. (IF 7.497) Pub Date : 2020-09-01
    Anthony King

    Live vaccines are gradually replaced by protein-based vaccines given the latter's better safety. But live vaccines seem to be more efficient via stimulation of the innate immune system.

  • Seeding sustainable education in developing countries: Teaching biotech in low-income areas.
    EMBO Rep. (IF 7.497) Pub Date : 2020-09-01
    Yensi Flores Bueso,Mark Tangney

    Synthetic biology has the potential to seed research in impoverished countries. Teaching students and academics has to take into account reality - lessons from Honduras.

  • Emerging pathogen evolution: Using evolutionary theory to understand the fate of novel infectious pathogens.
    EMBO Rep. (IF 7.497) Pub Date : 2020-08-30
    Camille Bonneaud,Ben Longdon

    Evolutionary biology is key to potentially predicting virulence and transmission after a pathogen jumps into a new host species. This knowledge would be valuable for designing public health strategies.

  • MicroRNA-195 controls MICU1 expression and tumor growth in ovarian cancer.
    EMBO Rep. (IF 7.497) Pub Date : 2020-08-27
    Geeta Rao,Shailendra Kumar Dhar Dwivedi,Yushan Zhang,Anindya Dey,Khader Shameer,Ramachandran Karthik,Subramanya Srikantan,Md Nazir Hossen,Jonathan D Wren,Muniswamy Madesh,Joel T Dudley,Resham Bhattacharya,Priyabrata Mukherjee

    MICU1 is a mitochondrial inner membrane protein that inhibits mitochondrial calcium entry; elevated MICU1 expression is characteristic of many cancers, including ovarian cancer. MICU1 induces both glycolysis and chemoresistance and is associated with poor clinical outcomes. However, there are currently no available interventions to normalize aberrant MICU1 expression. Here, we demonstrate that microRNA‐195‐5p

  • Mitochondrial transplantation-a possible therapeutic for mitochondrial dysfunction?: Mitochondrial transfer is a potential cure for many diseases but proof of efficacy and safety is still lacking.
    EMBO Rep. (IF 7.497) Pub Date : 2020-08-27
    Robert N Lightowlers,Zofia Ma Chrzanowska-Lightowlers,Oliver M Russell

    Transplantation of functional mitochondria directly into defective cells is a novel approach that has recently caught the attention of scientists and the general public alike. Could this be too good to be true?

  • Lamin A-mediated nuclear lamina integrity is required for proper ciliogenesis.
    EMBO Rep. (IF 7.497) Pub Date : 2020-08-19
    Jia-Rong Fan,Li-Ru You,Won-Jing Wang,Wei-Syun Huang,Ching-Tung Chu,Ya-Hui Chi,Hong-Chen Chen

    The primary cilium is a sensory organelle that receives specific signals from the extracellular environment important for vertebrate development and tissue homeostasis. Lamins, the major components of the nuclear lamina, are required to maintain the nuclear structure and are involved in most nuclear activities. In this study, we show that deficiency in lamin A/C causes defective ciliogenesis, accompanied

  • A cell atlas of adult muscle precursors uncovers early events in fibre-type divergence in Drosophila.
    EMBO Rep. (IF 7.497) Pub Date : 2020-08-19
    Maria Paula Zappia,Lucia de Castro,Majd M Ariss,Holly Jefferson,Abul Bmmk Islam,Maxim V Frolov

    In Drosophila, the wing disc‐associated muscle precursor cells give rise to the fibrillar indirect flight muscles (IFM) and the tubular direct flight muscles (DFM). To understand early transcriptional events underlying this muscle diversification, we performed single‐cell RNA‐sequencing experiments and built a cell atlas of myoblasts associated with third instar larval wing disc. Our analysis identified

  • Mobile students, remote education, free-fall economics: campus life in 2020: The pandemic-triggered economic crisis will have an unprecedented impact on higher education globally.
    EMBO Rep. (IF 7.497) Pub Date : 2020-08-19
    Howard Wolinsky

    Between decreased income and increasing expenses to move classes online, colleges and universities need to adapt to a pandemic-triggered severe and global recession.

  • Temporal activation of LRH‐1 and RAR‐γ in human pluripotent stem cells induces a functional naïve‐like state
    EMBO Rep. (IF 7.497) Pub Date : 2020-08-16
    Adeleh Taei; Tahereh Kiani; Zeinab Taghizadeh; Sharif Moradi; Azam Samadian; Sepideh Mollamohammadi; Ali Sharifi‐Zarchi; Stefan Guenther; Azimeh Akhlaghpour; Behrouz Asgari Abibeiglou; Mostafa Najar‐Asl; Razieh Karamzadeh; Keynoosh Khalooghi; Thomas Braun; Seyedeh‐Nafiseh Hassani; Hossein Baharvand

    Naïve pluripotency can be established in human pluripotent stem cells (hPSCs) by manipulation of transcription factors, signaling pathways, or a combination thereof. However, differences exist in the molecular and functional properties of naïve hPSCs generated by different protocols, which include varying similarities with pre‐implantation human embryos, differentiation potential, and maintenance of

  • Dynamics of Staphylococcus aureus Cas9 in DNA target Association and Dissociation.
    EMBO Rep. (IF 7.497) Pub Date : 2020-08-13
    Siqi Zhang,Qian Zhang,Xi-Miao Hou,Lijuan Guo,Fangzhu Wang,Lulu Bi,Xia Zhang,Hai-Hong Li,Fengcai Wen,Xu-Guang Xi,Xingxu Huang,Bin Shen,Bo Sun

    Staphylococcus aureus Cas9 (SaCas9) is an RNA‐guided endonuclease that targets complementary DNA adjacent to a protospacer adjacent motif (PAM) for cleavage. Its small size facilitates in vivo delivery for genome editing in various organisms. Herein, using single‐molecule and ensemble approaches, we systemically study the mechanism of SaCas9 underlying its interplay with DNA. We find that the DNA binding

  • Epstein-Barr virus-derived circular RNA LMP2A induces stemness in EBV-associated gastric cancer.
    EMBO Rep. (IF 7.497) Pub Date : 2020-08-12
    Li-Ping Gong,Jian-Ning Chen,Min Dong,Zhen-Dong Xiao,Zhi-Ying Feng,Yu-Hang Pan,Yu Zhang,Yu Du,Jing-Yue Zhang,Yuan-Hua Bi,Jun-Ting Huang,Jing Liang,Chun-Kui Shao

    Cancer stem cells (CSCs) are cancer‐initiating cells that are not only a source of tumorigenesis but also the cause of tumour progression, metastasis and therapy resistance. EBV‐associated gastric cancer (EBVaGC) is a distinct subtype of gastric cancer with unique clinicopathological and molecular features. However, whether CSCs exist in EBVaGC, and the tumorigenic mechanism of EBV, remains unclear

  • Non-canonical ATM/MRN activities temporally define the senescence secretory program.
    EMBO Rep. (IF 7.497) Pub Date : 2020-08-12
    Nicolas Malaquin,Marc-Alexandre Olivier,Aurélie Martinez,Stéphanie Nadeau,Christina Sawchyn,Jean-Philippe Coppé,Guillaume Cardin,Frédérick A Mallette,Judith Campisi,Francis Rodier

    Senescent cells display senescence‐associated (SA ) phenotypic programs such as stable proliferation arrest (SAPA ) and a secretory phenotype (SASP ). Senescence‐inducing persistent DNA double‐strand breaks (pDSB s) cause an immediate DNA damage response (DDR ) and SAPA , but the SASP requires days to develop. Here, we show that following the immediate canonical DDR , a delayed chromatin accumulation

  • The 18S rRNA m6 A methyltransferase METTL5 promotes mouse embryonic stem cell differentiation.
    EMBO Rep. (IF 7.497) Pub Date : 2020-08-11
    Ming Xing,Qi Liu,Cong Mao,Hanyi Zeng,Xin Zhang,Shuqin Zhao,Li Chen,Mingxi Liu,Bin Shen,Xuejiang Guo,Honghui Ma,Hao Chen,Jun Zhang

    RNA modifications represent a novel layer of regulation of gene expression. Functional experiments revealed that N6‐methyladenosine (m6A) on messenger RNA (mRNA ) plays critical roles in cell fate determination and development. m6A mark also resides in the decoding center of 18S ribosomal RNA (rRNA ); however, the biological function of m6A on 18S rRNA is still poorly understood. Here, we report that

  • Response by the authors.
    EMBO Rep. (IF 7.497) Pub Date : 2020-08-12
    Zhuang-Li Hu,Jian-Guo Chen,Fang Wang

    Response to comments on Cui Q-Q et al: "Hippocampal CD 39/ENTPD 1 promotes mouse depression-like behavior through hydrolyzing extracellular ATP".

  • Comments on Cui Q-Q et al: "Hippocampal CD 39/ENTPD 1 promotes mouse depression-like behavior …".
    EMBO Rep. (IF 7.497) Pub Date : 2020-08-12
    Herbert Zimmermann

    Comment on Hippocampal CD 39/ENTPD 1 promotes mouse depression-like behavior through hydrolyzing extracellular ATP by Cui et al.

  • Data protection during the coronavirus crisis.
    EMBO Rep. (IF 7.497) Pub Date : 2020-08-11
    Christophe Olivier Schneble,Bernice Simone Elger,David Martin Shaw

    Smartphone apps to track SARS-CoV 2 infections need to fulfill certain minimal requirements to guarantee privacy and justify their use under data protection laws.

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