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https://www.readbyqxmd.com/read/28438893/revealing-the-inner-workings-of-organoids
#1
Cristina Dias, François Guillemot
No abstract text is available yet for this article.
April 24, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28438892/brain-metabolism-in-health-aging-and%C3%A2-neurodegeneration
#2
REVIEW
Simonetta Camandola, Mark P Mattson
Brain cells normally respond adaptively to bioenergetic challenges resulting from ongoing activity in neuronal circuits, and from environmental energetic stressors such as food deprivation and physical exertion. At the cellular level, such adaptive responses include the "strengthening" of existing synapses, the formation of new synapses, and the production of new neurons from stem cells. At the molecular level, bioenergetic challenges result in the activation of transcription factors that induce the expression of proteins that bolster the resistance of neurons to the kinds of metabolic, oxidative, excitotoxic, and proteotoxic stresses involved in the pathogenesis of brain disorders including stroke, and Alzheimer's and Parkinson's diseases...
April 24, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28438891/a-second-wpl1-anti-cohesion-pathway-requires-dephosphorylation-of-fission-yeast-kleisin-rad21-by-pp4
#3
Adrien Birot, Karen Eguienta, Stéphanie Vazquez, Stéphane Claverol, Marc Bonneu, Karl Ekwall, Jean-Paul Javerzat, Sabine Vaur
Cohesin mediates sister chromatid cohesion which is essential for chromosome segregation and repair. Sister chromatid cohesion requires an acetyl-transferase (Eso1 in fission yeast) counteracting Wpl1, promoting cohesin release from DNA We report here that Wpl1 anti-cohesion function includes an additional mechanism. A genetic screen uncovered that Protein Phosphatase 4 (PP4) mutants allowed cell survival in the complete absence of Eso1. PP4 co-immunoprecipitated Wpl1 and cohesin and Wpl1 triggered Rad21 de-phosphorylation in a PP4-dependent manner...
April 24, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28438890/short-ftsz-filaments-can-drive-asymmetric-cell-envelope-constriction-at-the-onset-of-bacterial-cytokinesis
#4
Qing Yao, Andrew I Jewett, Yi-Wei Chang, Catherine M Oikonomou, Morgan Beeby, Cristina V Iancu, Ariane Briegel, Debnath Ghosal, Grant J Jensen
FtsZ, the bacterial homologue of eukaryotic tubulin, plays a central role in cell division in nearly all bacteria and many archaea. It forms filaments under the cytoplasmic membrane at the division site where, together with other proteins it recruits, it drives peptidoglycan synthesis and constricts the cell. Despite extensive study, the arrangement of FtsZ filaments and their role in division continue to be debated. Here, we apply electron cryotomography to image the native structure of intact dividing cells and show that constriction in a variety of Gram-negative bacterial cells, including Proteus mirabilis and Caulobacter crescentus, initiates asymmetrically, accompanied by asymmetric peptidoglycan incorporation and short FtsZ-like filament formation...
April 24, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28420744/the-transcription-factor-bzip14-regulates-the-tca-cycle-in-the-diatom-phaeodactylum-tricornutum
#5
Michiel Matthijs, Michele Fabris, Toshihiro Obata, Imogen Foubert, José Manuel Franco-Zorrilla, Roberto Solano, Alisdair R Fernie, Wim Vyverman, Alain Goossens
Diatoms are amongst the most important marine microalgae in terms of biomass, but little is known concerning the molecular mechanisms that regulate their versatile metabolism. Here, the pennate diatom Phaeodactylum tricornutum was studied at the metabolite and transcriptome level during nitrogen starvation and following imposition of three other stresses that impede growth. The coordinated upregulation of the tricarboxylic acid (TCA) cycle during the nitrogen stress response was the most striking observation...
April 18, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28420743/cancer-cell-metabolism-the-essential-role-of-the-nonessential-amino-acid-glutamine
#6
REVIEW
Ji Zhang, Natalya N Pavlova, Craig B Thompson
Biochemistry textbooks and cell culture experiments seem to be telling us two different things about the significance of external glutamine supply for mammalian cell growth and proliferation. Despite the fact that glutamine is a nonessential amino acid that can be synthesized by cells from glucose-derived carbons and amino acid-derived ammonia, most mammalian cells in tissue culture cannot proliferate or even survive in an environment that does not contain millimolar levels of glutamine. Not only are the levels of glutamine in standard tissue culture media at least ten-fold higher than other amino acids, but glutamine is also the most abundant amino acid in the human bloodstream, where it is assiduously maintained at approximately 0...
April 18, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28408439/sen1-has-unique-structural-features-grafted-on-the-architecture-of-the-upf1-like-helicase-family
#7
Bronislava Leonaitė, Zhong Han, Jérôme Basquin, Fabien Bonneau, Domenico Libri, Odil Porrua, Elena Conti
The superfamily 1B (SF1B) helicase Sen1 is an essential protein that plays a key role in the termination of non-coding transcription in yeast. Here, we identified the ~90 kDa helicase core of Saccharomyces cerevisiae Sen1 as sufficient for transcription termination in vitro and determined the corresponding structure at 1.8 Å resolution. In addition to the catalytic and auxiliary subdomains characteristic of the SF1B family, Sen1 has a distinct and evolutionarily conserved structural feature that "braces" the helicase core...
April 13, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28408438/prdm16-represses-the-type-i-interferon-response-in-adipocytes-to-promote-mitochondrial-and-thermogenic-programing
#8
Megan Kissig, Jeff Ishibashi, Matthew J Harms, Hee-Woong Lim, Rachel R Stine, Kyoung-Jae Won, Patrick Seale
Brown adipose has the potential to counteract obesity, and thus, identifying signaling pathways that regulate the activity of this tissue is of great clinical interest. PRDM16 is a transcription factor that activates brown fat-specific genes while repressing white fat and muscle-specific genes in adipocytes. Whether PRDM16 also controls other gene programs to regulate adipocyte function was unclear. Here, we identify a novel role for PRDM16 in suppressing type I interferon (IFN)-stimulated genes (ISGs), including Stat1, in adipocytes in vitro and in vivo Ectopic activation of type I IFN signaling in brown adipocytes induces mitochondrial dysfunction and reduces uncoupling protein 1 (UCP1) expression...
April 13, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28408437/the-myc-mrna-3-utr-couples-rna-polymerase-ii-function-to-glutamine-and-ribonucleotide-levels
#9
Francesca R Dejure, Nadine Royla, Steffi Herold, Jacqueline Kalb, Susanne Walz, Carsten P Ade, Guido Mastrobuoni, Jens T Vanselow, Andreas Schlosser, Elmar Wolf, Stefan Kempa, Martin Eilers
Deregulated expression of MYC enhances glutamine utilization and renders cell survival dependent on glutamine, inducing "glutamine addiction". Surprisingly, colon cancer cells that express high levels of MYC due to WNT pathway mutations are not glutamine-addicted but undergo a reversible cell cycle arrest upon glutamine deprivation. We show here that glutamine deprivation suppresses translation of endogenous MYC via the 3'-UTR of the MYC mRNA, enabling escape from apoptosis. This regulation is mediated by glutamine-dependent changes in adenosine-nucleotide levels...
April 13, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28404604/unusual-semi-extractability-as-a-hallmark-of-nuclear-body-associated-architectural-noncoding-rnas
#10
Takeshi Chujo, Tomohiro Yamazaki, Tetsuya Kawaguchi, Satoshi Kurosaka, Toru Takumi, Shinichi Nakagawa, Tetsuro Hirose
NEAT1_2 long noncoding RNA (lncRNA) is the molecular scaffold of paraspeckle nuclear bodies. Here, we report an improved RNA extraction method: extensive needle shearing or heating of cell lysate in RNA extraction reagent improved NEAT1_2 extraction by 20-fold (a property we term "semi-extractability"), whereas using a conventional method NEAT1_2 was trapped in the protein phase. The improved extraction method enabled us to estimate that approximately 50 NEAT1_2 molecules are present in a single paraspeckle...
April 12, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28400401/trail-and-tnf-induced-signaling-complexes-so-similar-yet-so-different
#11
Harald Wajant
No abstract text is available yet for this article.
April 11, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28396493/cut-in-translation-ribosome-dependent-mrna-decay
#12
David Lalaouna, Eric Massé
Transcription and translation are two complex mechanisms that are tightly coupled in prokaryotic cells. Even before the completion of transcription, ribosomes attach to the nascent mRNA and initiate protein synthesis. Remarkably, recent publications have indicated an association between translation and decay of certain mRNAs. In this issue of The EMBO Journal, Leroy et al (2017) depicts a fascinating mechanism of mRNA degradation, which involves the ribosome-associated ribonuclease Rae1 in Bacillus subtilis In a translation-dependent manner, Rae1 binds the ribosomal aminoacylation (A)-site and cleaves between specific codons of the targeted mRNA...
April 10, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28377464/stard3-mediates-endoplasmic-reticulum-to-endosome-cholesterol-transport-at-membrane-contact-sites
#13
Léa P Wilhelm, Corinne Wendling, Benoît Védie, Toshihide Kobayashi, Marie-Pierre Chenard, Catherine Tomasetto, Guillaume Drin, Fabien Alpy
StAR-related lipid transfer domain-3 (STARD3) is a sterol-binding protein that creates endoplasmic reticulum (ER)-endosome contact sites. How this protein, at the crossroad between sterol uptake and synthesis pathways, impacts the intracellular distribution of this lipid was ill-defined. Here, by using in situ cholesterol labeling and quantification, we demonstrated that STARD3 induces cholesterol accumulation in endosomes at the expense of the plasma membrane. STARD3-mediated cholesterol routing depends both on its lipid transfer activity and its ability to create ER-endosome contacts...
April 4, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28377463/fatty-acid-synthesis-is-critical-for-stem-cell-pluripotency-via-promoting-mitochondrial-fission
#14
Lihua Wang, Tong Zhang, Lin Wang, Yongping Cai, Xiuying Zhong, Xiaoping He, Lan Hu, Shengya Tian, Mian Wu, Lijian Hui, Huafeng Zhang, Ping Gao
Pluripotent stem cells are known to display distinct metabolic phenotypes than their somatic counterparts. While accumulating studies are focused on the roles of glucose and amino acid metabolism in facilitating pluripotency, little is known regarding the role of lipid metabolism in regulation of stem cell activities. Here, we show that fatty acid (FA) synthesis activation is critical for stem cell pluripotency. Our initial observations demonstrated enhanced lipogenesis in pluripotent cells and during cellular reprogramming...
April 4, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28377462/an-aberrant-phase-transition-of-stress-granules-triggered-by-misfolded-protein-and-prevented-by-chaperone-function
#15
Daniel Mateju, Titus M Franzmann, Avinash Patel, Andrii Kopach, Edgar E Boczek, Shovamayee Maharana, Hyun O Lee, Serena Carra, Anthony A Hyman, Simon Alberti
Stress granules (SG) are membrane-less compartments involved in regulating mRNAs during stress. Aberrant forms of SGs have been implicated in age-related diseases, such as amyotrophic lateral sclerosis (ALS), but the molecular events triggering their formation are still unknown. Here, we find that misfolded proteins, such as ALS-linked variants of SOD1, specifically accumulate and aggregate within SGs in human cells. This decreases the dynamics of SGs, changes SG composition, and triggers an aberrant liquid-to-solid transition of in vitro reconstituted compartments...
April 4, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28373211/a-new-sub-pathway-of-long-patch-base-excision-repair-involving-5-gap-formation
#16
Jordan Woodrick, Suhani Gupta, Sharon Camacho, Swetha Parvathaneni, Sujata Choudhury, Amrita Cheema, Yi Bai, Pooja Khatkar, Hayriye Verda Erkizan, Furqan Sami, Yan Su, Orlando D Schärer, Sudha Sharma, Rabindra Roy
Base excision repair (BER) is one of the most frequently used cellular DNA repair mechanisms and modulates many human pathophysiological conditions related to DNA damage. Through live cell and in vitro reconstitution experiments, we have discovered a major sub-pathway of conventional long-patch BER that involves formation of a 9-nucleotide gap 5' to the lesion. This new sub-pathway is mediated by RECQ1 DNA helicase and ERCC1-XPF endonuclease in cooperation with PARP1 poly(ADP-ribose) polymerase and RPA The novel gap formation step is employed during repair of a variety of DNA lesions, including oxidative and alkylation damage...
April 3, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28363943/rae1-yacp-a-new-endoribonuclease-involved-in%C3%A2-ribosome-dependent-mrna-decay-in-bacillus%C3%A2-subtilis
#17
Magali Leroy, Jérémie Piton, Laetitia Gilet, Olivier Pellegrini, Caroline Proux, Jean-Yves Coppée, Sabine Figaro, Ciarán Condon
The PIN domain plays a central role in cellular RNA biology and is involved in processes as diverse as rRNA maturation, mRNA decay and telomerase function. Here, we solve the crystal structure of the Rae1 (YacP) protein of Bacillus subtilis, a founding member of the NYN (Nedd4-BP1/YacP nuclease) subfamily of PIN domain proteins, and identify potential substrates in vivo Unexpectedly, degradation of a characterised target mRNA was completely dependent on both its translation and reading frame. We provide evidence that Rae1 associates with the B...
March 31, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28363942/usp49-negatively-regulates-tumorigenesis-and-chemoresistance-through-fkbp51-akt-signaling
#18
Kuntian Luo, Yunhui Li, Yujiao Yin, Lei Li, Chenming Wu, Yuping Chen, Somaira Nowsheen, Qi Hu, Lizhi Zhang, Zhenkun Lou, Jian Yuan
The AKT pathway is a fundamental signaling pathway that mediates multiple cellular processes, such as cell proliferation and survival, angiogenesis, and glucose metabolism. We recently reported that the immunophilin FKBP51 is a scaffolding protein that can enhance PHLPP-AKT interaction and facilitate PHLPP-mediated dephosphorylation of AKT at Ser473, negatively regulating AKT activation. However, the regulation of FKBP51-PHLPP-AKT pathway remains unclear. Here we report that a deubiquitinase, USP49, is a new regulator of the AKT pathway...
March 31, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28348166/mfn2-is-critical-for-brown-adipose-tissue-thermogenic-function
#19
Marie Boutant, Sameer S Kulkarni, Magali Joffraud, Joanna Ratajczak, Miriam Valera-Alberni, Roy Combe, Antonio Zorzano, Carles Cantó
Mitochondrial fusion and fission events, collectively known as mitochondrial dynamics, act as quality control mechanisms to ensure mitochondrial function and fine-tune cellular bioenergetics. Defective mitofusin 2 (Mfn2) expression and enhanced mitochondrial fission in skeletal muscle are hallmarks of insulin-resistant states. Interestingly, Mfn2 is highly expressed in brown adipose tissue (BAT), yet its role remains unexplored. Using adipose-specific Mfn2 knockout (Mfn2-adKO) mice, we demonstrate that Mfn2, but not Mfn1, deficiency in BAT leads to a profound BAT dysfunction, associated with impaired respiratory capacity and a blunted response to adrenergic stimuli...
March 27, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28336683/let-7-regulates-radial-migration-of-new-born-neurons-through-positive-regulation-of-autophagy
#20
Rebecca Petri, Karolina Pircs, Marie E Jönsson, Malin Åkerblom, Per Ludvik Brattås, Thies Klussendorf, Johan Jakobsson
During adult neurogenesis, newly formed olfactory bulb (OB) interneurons migrate radially to integrate into specific layers of the OB Despite the importance of this process, the intracellular mechanisms that regulate radial migration remain poorly understood. Here, we find that microRNA (miRNA) let-7 regulates radial migration by modulating autophagy in new-born neurons. Using Argonaute2 immunoprecipitation, we performed global profiling of miRNAs in adult-born OB neurons and identified let-7 as a highly abundant miRNA family...
March 23, 2017: EMBO Journal
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