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https://www.readbyqxmd.com/read/28935685/new-functions-in-translation-termination-uncovered-for-nmd-factor-upf3b
#1
Oliver Mühlemann, Evangelos D Karousis
No abstract text is available yet for this article.
September 21, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28931563/molecular-cartography-of-mutational-landscapes-in-melanomas
#2
Emily C Beckwitt, Bennett Van Houten
No abstract text is available yet for this article.
September 20, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28928204/bone-morphogenetic-protein-and-retinoic-acid-synergistically-specify-female-germ-cell-fate-in-mice
#3
Hidetaka Miyauchi, Hiroshi Ohta, So Nagaoka, Fumio Nakaki, Kotaro Sasaki, Katsuhiko Hayashi, Yukihiro Yabuta, Tomonori Nakamura, Takuya Yamamoto, Mitinori Saitou
The mechanism for sex determination in mammalian germ cells remains unclear. Here, we reconstitute the female sex determination in mouse germ cells in vitro under a defined condition without the use of gonadal somatic cells. We show that retinoic acid (RA) and its key effector, STRA8, are not sufficient to induce the female germ-cell fate. In contrast, bone morphogenetic protein (BMP) and RA synergistically induce primordial germ cells (PGCs)/PGC-like cells (PGCLCs) derived from embryonic stem cells (ESCs) into fetal primary oocytes...
September 19, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28923826/structure-of-a-vird4-coupling-protein-bound-to-a-virb-type-iv-secretion-machinery
#4
Adam Redzej, Marta Ukleja, Sarah Connery, Martina Trokter, Catarina Felisberto-Rodrigues, Adam Cryar, Konstantinos Thalassinos, Richard D Hayward, Elena V Orlova, Gabriel Waksman
Type IV secretion (T4S) systems are versatile bacterial secretion systems mediating transport of protein and/or DNA T4S systems are generally composed of 11 VirB proteins and 1 VirD protein (VirD4). The VirB1-11 proteins assemble to form a secretion machinery and a pilus while the VirD4 protein is responsible for substrate recruitment. The structure of VirD4 in isolation is known; however, its structure bound to the VirB1-11 apparatus has not been determined. Here, we purify a T4S system with VirD4 bound, define the biochemical requirements for complex formation and describe the protein-protein interaction network in which VirD4 is involved...
September 18, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28923825/qualitative-differences-in-t-cell-activation-by-dendritic-cell-derived-extracellular-vesicle-subtypes
#5
Mercedes Tkach, Joanna Kowal, Andres E Zucchetti, Lotte Enserink, Mabel Jouve, Danielle Lankar, Michael Saitakis, Lorena Martin-Jaular, Clotilde Théry
Exosomes, nano-sized secreted extracellular vesicles (EVs), are actively studied for their diagnostic and therapeutic potential. In particular, exosomes secreted by dendritic cells (DCs) have been shown to carry MHC-peptide complexes allowing efficient activation of T lymphocytes, thus displaying potential as promoters of adaptive immune responses. DCs also secrete other types of EVs of different size, subcellular origin and protein composition, whose immune capacities have not been yet compared to those of exosomes...
September 18, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28923824/snapin-promotes-hiv-1-transmission-from-dendritic-cells-by-dampening-tlr8-signaling
#6
Elham Khatamzas, Madeleine Maria Hipp, Daniel Gaughan, Tica Pichulik, Alasdair Leslie, Ricardo A Fernandes, Daniele Muraro, Sarah Booth, Kieran Zausmer, Mei-Yi Sun, Benedikt Kessler, Sarah Rowland-Jones, Vincenzo Cerundolo, Alison Simmons
HIV-1 traffics through dendritic cells (DCs) en route to establishing a productive infection in T lymphocytes but fails to induce an innate immune response. Within DC endosomes, HIV-1 somehow evades detection by the pattern-recognition receptor (PRR) Toll-like receptor 8 (TLR8). Using a phosphoproteomic approach, we identified a robust and diverse signaling cascade triggered by HIV-1 upon entry into human DCs. A secondary siRNA screen of the identified signaling factors revealed several new mediators of HIV-1 trans-infection of CD4(+) T cells in DCs, including the dynein motor protein Snapin...
September 18, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28923823/forming-a-link-between-ptsd-and-ad
#7
Johannes Gräff
No abstract text is available yet for this article.
September 18, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28916614/dysregulated-molecular-pathways-in-amyotrophic-lateral-sclerosis-frontotemporal-dementia-spectrum-disorder
#8
REVIEW
Fen-Biao Gao, Sandra Almeida, Rodrigo Lopez-Gonzalez
Frontotemporal dementia (FTD), the second most common form of dementia in people under 65 years of age, is characterized by progressive atrophy of the frontal and/or temporal lobes. FTD overlaps extensively with the motor neuron disease amyotrophic lateral sclerosis (ALS), especially at the genetic level. Both FTD and ALS can be caused by many mutations in the same set of genes; the most prevalent of these mutations is a GGGGCC repeat expansion in the first intron of C9ORF72 As shown by recent intensive studies, some key cellular pathways are dysregulated in the ALS-FTD spectrum disorder, including autophagy, nucleocytoplasmic transport, DNA damage repair, pre-mRNA splicing, stress granule dynamics, and others...
September 15, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28899900/ret-receptor-tyrosine-kinase-sustains-proliferation-and-tissue-maturation-in-intestinal-epithelia
#9
Daniel Perea, Jordi Guiu, Bruno Hudry, Chrysoula Konstantinidou, Alexandra Milona, Dafni Hadjieconomou, Thomas Carroll, Nina Hoyer, Dipa Natarajan, Jukka Kallijärvi, James A Walker, Peter Soba, Nikhil Thapar, Alan J Burns, Kim B Jensen, Irene Miguel-Aliaga
Expression of the Ret receptor tyrosine kinase is a defining feature of enteric neurons. Its importance is underscored by the effects of its mutation in Hirschsprung disease, leading to absence of gut innervation and severe gastrointestinal symptoms. We report a new and physiologically significant site of Ret expression in the intestine: the intestinal epithelium. Experiments in Drosophila indicate that Ret is expressed both by enteric neurons and adult intestinal epithelial progenitors, which require Ret to sustain their proliferation...
September 12, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28899899/dual-function-of-upf3b-in-early-and-late-translation-termination
#10
Gabriele Neu-Yilik, Etienne Raimondeau, Boris Eliseev, Lahari Yeramala, Beate Amthor, Aurélien Deniaud, Karine Huard, Kathrin Kerschgens, Matthias W Hentze, Christiane Schaffitzel, Andreas E Kulozik
Nonsense-mediated mRNA decay (NMD) is a cellular surveillance pathway that recognizes and degrades mRNAs with premature termination codons (PTCs). The mechanisms underlying translation termination are key to the understanding of RNA surveillance mechanisms such as NMD and crucial for the development of therapeutic strategies for NMD-related diseases. Here, we have used a fully reconstituted in vitro translation system to probe the NMD proteins for interaction with the termination apparatus. We discovered that UPF3B (i) interacts with the release factors, (ii) delays translation termination and (iii) dissociates post-termination ribosomal complexes that are devoid of the nascent peptide...
September 12, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28882847/epigenetic-regulation-of-left-right-asymmetry-by-dna-methylation
#11
Lu Wang, Zhibin Liu, Hao Lin, Dongyuan Ma, Qinghua Tao, Feng Liu
DNA methylation is a major epigenetic modification; however, the precise role of DNA methylation in vertebrate development is still not fully understood. Here, we show that DNA methylation is essential for the establishment of the left-right (LR) asymmetric body plan during vertebrate embryogenesis. Perturbation of DNA methylation by depletion of DNA methyltransferase 1 (dnmt1) or dnmt3bb.1 in zebrafish embryos leads to defects in dorsal forerunner cell (DFC) specification or collective migration, laterality organ malformation, and disruption of LR patterning...
September 7, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28877996/blm-and-slx4-play-opposing-roles-in-recombination-dependent-replication-at-human-telomeres
#12
Alexander P Sobinoff, Joshua Am Allen, Axel A Neumann, Sile F Yang, Monica E Walsh, Jeremy D Henson, Roger R Reddel, Hilda A Pickett
Alternative lengthening of telomeres (ALT) is a telomere lengthening pathway that predominates in aggressive tumors of mesenchymal origin; however, the underlying mechanism of telomere synthesis is not fully understood. Here, we show that the BLM-TOP3A-RMI (BTR) dissolvase complex is required for ALT-mediated telomere synthesis. We propose that recombination intermediates formed during strand invasion are processed by the BTR complex, initiating rapid and extensive POLD3-dependent telomere synthesis followed by dissolution, with no overall exchange of telomeric DNA...
September 6, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28871058/the-hox-proteins-ubx-and-abda-collaborate-with-the-transcription-pausing-factor-m1bp-to-regulate-gene-transcription
#13
Amel Zouaz, Ankush Auradkar, Marie Claire Delfini, Meiggie Macchi, Marine Barthez, Serge Ela Akoa, Leila Bastianelli, Gengqiang Xie, Wu-Min Deng, Stuart S Levine, Yacine Graba, Andrew J Saurin
In metazoans, the pausing of RNA polymerase II at the promoter (paused Pol II) has emerged as a widespread and conserved mechanism in the regulation of gene transcription. While critical in recruiting Pol II to the promoter, the role transcription factors play in transitioning paused Pol II into productive Pol II is, however, little known. By studying how Drosophila Hox transcription factors control transcription, we uncovered a molecular mechanism that increases productive transcription. We found that the Hox proteins AbdA and Ubx target gene promoters previously bound by the transcription pausing factor M1BP, containing paused Pol II and enriched with promoter-proximal Polycomb Group (PcG) proteins, yet lacking the classical H3K27me3 PcG signature...
September 4, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28864543/structural-basis-for-antibacterial-peptide-self-immunity-by-the-bacterial-abc-transporter-mcjd
#14
Kiran Bountra, Gregor Hagelueken, Hassanul G Choudhury, Valentina Corradi, Kamel El Omari, Armin Wagner, Indran Mathavan, Séverine Zirah, Weixiao Yuan Wahlgren, D Peter Tieleman, Olav Schiemann, Sylvie Rebuffat, Konstantinos Beis
Certain pathogenic bacteria produce and release toxic peptides to ensure either nutrient availability or evasion from the immune system. These peptides are also toxic to the producing bacteria that utilize dedicated ABC transporters to provide self-immunity. The ABC transporter McjD exports the antibacterial peptide MccJ25 in Escherichia coli Our previously determined McjD structure provided some mechanistic insights into antibacterial peptide efflux. In this study, we have determined its structure in a novel conformation, apo inward-occluded and a new nucleotide-bound state, high-energy outward-occluded intermediate state, with a defined ligand binding cavity...
September 1, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28864542/somatodendritic-accumulation-of-tau-in-alzheimer-s-disease-is-promoted-by-fyn-mediated-local-protein-translation
#15
Chuanzhou Li, Jürgen Götz
The cause of protein accumulation in neurodegenerative disease is incompletely understood. In Alzheimer's disease (AD), the axonally enriched protein Tau forms hyperphosphorylated aggregates in the somatodendritic domain. Consequently, a process of subcellular relocalization driven by Tau phosphorylation and detachment from microtubules has been proposed. Here, we reveal an alternative mechanism of de novo protein synthesis of Tau and its hyperphosphorylation in the somatodendritic domain, induced by oligomeric amyloid-β (Aβ) and mediated by the kinase Fyn that activates the ERK/S6 signaling pathway...
September 1, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28838936/redox-regulation-of-plant-stem-cell-fate
#16
Jian Zeng, Zhicheng Dong, Haijun Wu, Zhaoxia Tian, Zhong Zhao
Despite the importance of stem cells in plant and animal development, the common mechanisms of stem cell maintenance in both systems have remained elusive. Recently, the importance of hydrogen peroxide (H2O2) signaling in priming stem cell differentiation has been extensively studied in animals. Here, we show that different forms of reactive oxygen species (ROS) have antagonistic roles in plant stem cell regulation, which were established by distinct spatiotemporal patterns of ROS-metabolizing enzymes. The superoxide anion (O2·-) is markedly enriched in stem cells to activate WUSCHEL and maintain stemness, whereas H2O2 is more abundant in the differentiating peripheral zone to promote stem cell differentiation...
August 24, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28838935/noise-in-a-phosphorelay-drives-stochastic-entry-into-sporulation-in-bacillus-subtilis
#17
Jonathan R Russell, Matthew T Cabeen, Paul A Wiggins, Johan Paulsson, Richard Losick
Entry into sporulation in Bacillus subtilis is governed by a phosphorelay in which phosphoryl groups from a histidine kinase are successively transferred via relay proteins to the response regulator Spo0A. Spo0A~P, in turn, sets in motion events that lead to asymmetric division and activation of the cell-specific transcription factor σ(F), a hallmark for entry into sporulation. Here, we have used a microfluidics-based platform to investigate the activation of Spo0A and σ(F) in individual cells held under constant, sporulation-inducing conditions...
August 24, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28814448/carcinogen-susceptibility-is-regulated-by-genome-architecture-and-predicts-cancer-mutagenesis
#18
Pablo E García-Nieto, Erin K Schwartz, Devin A King, Jonas Paulsen, Philippe Collas, Rafael E Herrera, Ashby J Morrison
The development of many sporadic cancers is directly initiated by carcinogen exposure. Carcinogens induce malignancies by creating DNA lesions (i.e., adducts) that can result in mutations if left unrepaired. Despite this knowledge, there has been remarkably little investigation into the regulation of susceptibility to acquire DNA lesions. In this study, we present the first quantitative human genome-wide map of DNA lesions induced by ultraviolet (UV) radiation, the ubiquitous carcinogen in sunlight that causes skin cancer...
August 16, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28801509/exosome-cofactor-hmtr4-competes-with-export-adaptor-alyref-to-ensure-balanced-nuclear-rna-pools-for-degradation-and-export
#19
Jing Fan, Bin Kuai, Guifen Wu, Xudong Wu, Binkai Chi, Lantian Wang, Ke Wang, Zhubing Shi, Heng Zhang, She Chen, Zhisong He, Siyuan Wang, Zhaocai Zhou, Guohui Li, Hong Cheng
The exosome is a key RNA machine that functions in the degradation of unwanted RNAs. Here, we found that significant fractions of precursors and mature forms of mRNAs and long noncoding RNAs are degraded by the nuclear exosome in normal human cells. Exosome-mediated degradation of these RNAs requires its cofactor hMTR4. Significantly, hMTR4 plays a key role in specifically recruiting the exosome to its targets. Furthermore, we provide several lines of evidence indicating that hMTR4 executes this role by directly competing with the mRNA export adaptor ALYREF for associating with ARS2, a component of the cap-binding complex (CBC), and this competition is critical for determining whether an RNA is degraded or exported to the cytoplasm...
August 11, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28790177/phosphorylation-of-the-fus-low-complexity-domain-disrupts-phase-separation-aggregation-and-toxicity
#20
Zachary Monahan, Veronica H Ryan, Abigail M Janke, Kathleen A Burke, Shannon N Rhoads, Gül H Zerze, Robert O'Meally, Gregory L Dignon, Alexander E Conicella, Wenwei Zheng, Robert B Best, Robert N Cole, Jeetain Mittal, Frank Shewmaker, Nicolas L Fawzi
Neuronal inclusions of aggregated RNA-binding protein fused in sarcoma (FUS) are hallmarks of ALS and frontotemporal dementia subtypes. Intriguingly, FUS's nearly uncharged, aggregation-prone, yeast prion-like, low sequence-complexity domain (LC) is known to be targeted for phosphorylation. Here we map in vitro and in-cell phosphorylation sites across FUS LC We show that both phosphorylation and phosphomimetic variants reduce its aggregation-prone/prion-like character, disrupting FUS phase separation in the presence of RNA or salt and reducing FUS propensity to aggregate...
August 8, 2017: EMBO Journal
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