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https://www.readbyqxmd.com/read/27899360/widespread-and-dynamic-translational-control-of-red-blood-cell-development
#1
Juan R Alvarez-Dominguez, Xu Zhang, Wenqian Hu
Cell development requires tight yet dynamic control of protein production. Here, we use parallel RNA and ribosome profiling to study translational regulatory dynamics during murine terminal erythropoiesis. We uncover pervasive translational control of protein synthesis, including widespread alternative translation initiation and termination, robust discrimination of long non-coding from micropeptide-encoding RNAs, and dynamic use of upstream reading frames. We further identify hundreds of mRNAs whose translation efficiency is dynamically controlled during erythropoiesis, and find that they enrich for target sites of RNA-binding proteins that are hematopoietic cell-specific, thus unraveling potential regulators of erythroid translational programs...
November 29, 2016: Blood
https://www.readbyqxmd.com/read/27858515/eif4b-stimulates-eif4a-atpase-and-unwinding-activities-by-direct-interaction-through-its-7-repeats-region
#2
Alexandra Zoi Andreou, Ulf Harms, Dagmar Klostermeier
Eukaryotic translation initiation starts with binding of the eIF4F complex to the 5'-m7G cap of the mRNA. Recruitment of the 43S pre-initiation complex (PIC), formed by the 40S ribosomal subunit and other translation initiation factors, leads to formation of the 48S PIC that then scans the 5'-untranslated region (5'-UTR) towards the start codon. The eIF4F complex consists of eIF4E, the cap binding protein, eIF4A, a DEAD-box RNA helicase that is believed to unwind secondary structures in the 5'UTR during scanning, and eIF4G, a scaffold protein that binds to both eIF4E and eIF4A...
November 18, 2016: RNA Biology
https://www.readbyqxmd.com/read/27833593/recessive-resistance-to-plant-viruses-potential-resistance-genes-beyond-translation-initiation-factors
#3
REVIEW
Masayoshi Hashimoto, Yutaro Neriya, Yasuyuki Yamaji, Shigetou Namba
The ability of plant viruses to propagate their genomes in host cells depends on many host factors. In the absence of an agrochemical that specifically targets plant viral infection cycles, one of the most effective methods for controlling viral diseases in plants is taking advantage of the host plant's resistance machinery. Recessive resistance is conferred by a recessive gene mutation that encodes a host factor critical for viral infection. It is a branch of the resistance machinery and, as an inherited characteristic, is very durable...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27824302/new-insights-into-the-topology-of-the-scanning-ribosome-during-translation-initiation-lessons-from-viruses
#4
René Toribio, Irene Díaz-López, Iván Ventoso
Location of the translation initiation codon generally requires scanning of the 43S ribosomal preinitiation complex (43S PIC) from the 5' of the mRNA. Associated RNA helicases can facilitate movement of the 43S PIC by removing secondary structure present in the 5' UTR of mRNA, which is required for codon inspection. The canonical RNA-dependent helicase eIF4A is directly involved in this process, as part of the eIF4F complex (eIF4G+eIF4A+eIF4E) that associates first with mRNA and then recruits the 43S PIC to initiate scanning...
November 8, 2016: RNA Biology
https://www.readbyqxmd.com/read/27773676/the-structures-of-eif4e-eif4g-complexes-reveal-an-extended-interface-to-regulate-translation-initiation
#5
Stefan Grüner, Daniel Peter, Ramona Weber, Lara Wohlbold, Min-Yi Chung, Oliver Weichenrieder, Eugene Valkov, Cátia Igreja, Elisa Izaurralde
Eukaryotic initiation factor 4G (eIF4G) plays a central role in translation initiation through its interactions with the cap-binding protein eIF4E. This interaction is a major drug target for repressing translation and is naturally regulated by 4E-binding proteins (4E-BPs). 4E-BPs and eIF4G compete for binding to the eIF4E dorsal surface via a shared canonical 4E-binding motif, but also contain auxiliary eIF4E-binding sequences, which were assumed to contact non-overlapping eIF4E surfaces. However, it is unknown how metazoan eIF4G auxiliary sequences bind eIF4E...
October 19, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27771839/transcriptome-and-proteome-oriented-identification-of-dysregulated-eif4g-stat3-and-hippo-pathways-altered-by-pik3ca-h1047r-in-her2-er-positive-breast-cancer
#6
Feixiong Cheng, Junfei Zhao, Ariella B Hanker, Monica Red Brewer, Carlos L Arteaga, Zhongming Zhao
PURPOSE: Phosphatidylinositol 3-kinase (PI3K)/AKT pathway aberrations are common in human breast cancer. Furthermore, PIK3CA mutations are commonly associated with resistance to anti-epidermal growth factor receptor 2 (HER2) or anti-estrogen receptor (ER) agents in HER2 or ER positive (HER2(+)/ER(+)) breast cancer. Hence, deciphering the underlying mechanisms of PIK3CA mutations in HER2(+)/ER(+) breast cancer would provide novel insights into elucidating resistance to anti-HER2/ER therapies...
October 22, 2016: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/27749759/restorative-mechanisms-regulating-protein-balance-in-skeletal-muscle-during-recovery-from-sepsis
#7
Kristen T Crowell, David I Soybel, Charles H Lang
Muscle deconditioning is commonly observed in patients surviving sepsis. Little is known regarding the molecular mechanisms regulating muscle protein homeostasis during the recovery or convalescence phase. We adapted a sepsis-recovery mouse model that uses cecal ligation and puncture (CLP), followed 24 h later by cecal resection and antibiotic treatment, to identify putative cellular pathways regulating protein synthesis and breakdown in skeletal muscle. Ten days after CLP, body weight and food consumption did not differ between control and sepsis-recovery mice, but gastrocnemius weight was reduced...
October 5, 2016: Shock
https://www.readbyqxmd.com/read/27748944/hpip-promotes-gastric-cancer-cell-proliferation-through-activation-of-cap-dependent-translation
#8
Bing Chen, Jin Zhao, Shengbin Zhang, Yonggang Zhang, Zonghai Huang
Cap-dependent translation has an essential role in the control of cell proliferation by initiating the translation of oncogenes involved in the regulation of cell cycle progression, such as cyclin D1, and its deregulation contributes to the development and progression of various types of cancers. Hematopoietic pre-B-cell leukemia transcription factor interacting protein (HPIP) was found to be overexpressed in gastric cancer (GC) tissues compared to normal tissues and to promote GC growth in vitro and in vivo...
October 11, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27714564/heat-shock-protein-27-hsp27-regulates-stat3-and-eif4g-levels-in-first-trimester-human-placenta
#9
Gali Epstein Shochet, Oded Komemi, Dana Sadeh-Mestechkin, Meir Pomeranz, Ami Fishman, Liat Drucker, Michael Lishner, Shelly Tartakover Matalon
During placental implantation, cytotrophoblast cells differentiate to extravillous trophoblast (EVT) cells that invade from the placenta into the maternal uterine blood vessels. The heat shock protein-27 (HSP27), the signal transducer and activator of transcription-3 (STAT3) and the eukaryotic translation initiation factor 4E (EIF4E) are involved in regulating EVT cell differentiation/migration. EIF4E and EIF4G compose the translation initiation complex, which is a major control point in protein translation...
October 6, 2016: Journal of Molecular Histology
https://www.readbyqxmd.com/read/27694156/eif4g-an-integrator-of-mrna-metabolism
#10
Satarupa Das, Biswadip Das
The eukaryotic translation initiation factor, eIF4G, plays a key functional role in the initiation of cap-dependent translation by acting as an adapter to nucleate the assembly of eIF4F complex. Together with poly(A)-binding protein and eIF3, eIF4F subsequently triggers the recruitment of 43S ribosomal pre-initiation complex to the messenger RNA template. Since eukaryotes primarily regulate translation at the level of initiation, eIF4G is implicated in the control of eukaryotic gene expression. Remarkably, emerging evidence in Saccharomyces cerevisiae indicates that eIF4G also plays a key role in nuclear mRNA biogenesis and surveillance-a finding that is in agreement with its nuclear distribution...
November 2016: FEMS Yeast Research
https://www.readbyqxmd.com/read/27624100/leucine-supplementation-stimulates-protein-synthesis-and-reduces-degradation-signal-activation-in-muscle-of-newborn-pigs-during-acute-endotoxemia
#11
Adriana D Hernandez-García, Daniel A Columbus, Rodrigo Manjarín, Hanh V Nguyen, Agus Suryawan, Renán A Orellana, Teresa A Davis
Sepsis disrupts skeletal muscle proteostasis and mitigates the anabolic response to leucine (Leu) in muscle of mature animals. We have shown that Leu stimulates muscle protein synthesis (PS) in healthy neonatal piglets. To determine if supplemental Leu can stimulate PS and reduce protein degradation (PD) signaling in neonatal muscle during endotoxemia, overnight-fasted neonatal pigs were infused for 8 h with LPS or saline while plasma amino acids, glucose, and insulin were maintained at fasting levels during pancreatic-substrate clamps...
October 1, 2016: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27613419/arginine-methylation-promotes-translation-repression-activity-of-eif4g-binding-protein-scd6
#12
Gopalakrishna Poornima, Shanaya Shah, Venkadasubramanian Vignesh, Roy Parker, Purusharth I Rajyaguru
Regulation of translation plays a critical role in determining mRNA fate. A new role was recently reported for a subset of RGG-motif proteins in repressing translation initiation by binding eIF4G1. However the signaling mechanism(s) that leads to spatial and temporal regulation of repression activity of RGG-motif proteins remains unknown. Here we report the role of arginine methylation in regulation of repression activity of Scd6, a conserved RGG-motif protein. We demonstrate that Scd6 gets arginine methylated at its RGG-motif and Hmt1 plays an important role in its methylation...
November 2, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27601676/eif4b-stimulates-translation-of-long-mrnas-with-structured-5-utrs-and-low-closed-loop-potential-but-weak-dependence-on-eif4g
#13
Neelam Dabas Sen, Fujun Zhou, Michael S Harris, Nicholas T Ingolia, Alan G Hinnebusch
DEAD-box RNA helicases eukaryotic translation initiation factor 4A (eIF4A) and Ded1 promote translation by resolving mRNA secondary structures that impede preinitiation complex (PIC) attachment to mRNA or scanning. Eukaryotic translation initiation factor 4B (eIF4B) is a cofactor for eIF4A but also might function independently of eIF4A. Ribosome profiling of mutants lacking eIF4B or with impaired eIF4A or Ded1 activity revealed that eliminating eIF4B reduces the relative translational efficiencies of many more genes than does inactivation of eIF4A, despite comparable reductions in bulk translation, and few genes display unusually strong requirements for both factors...
September 20, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27578149/distinct-recruitment-of-human-eif4e-isoforms-to-processing-bodies-and-stress-granules
#14
Klara Frydryskova, Tomas Masek, Katerina Borcin, Silvia Mrvova, Veronica Venturi, Martin Pospisek
BACKGROUND: Eukaryotic translation initiation factor 4E (eIF4E) plays a pivotal role in the control of cap-dependent translation initiation, modulates the fate of specific mRNAs, occurs in processing bodies (PBs) and is required for formation of stress granules (SGs). In this study, we focused on the subcellular localization of a representative compendium of eIF4E protein isoforms, particularly on the less studied members of the human eIF4E protein family, eIF4E2 and eIF4E3. RESULTS: We showed that unlike eIF4E1, its less studied isoform eIF4E3_A, encoded by human chromosome 3, localized to stress granules but not PBs upon both heat shock and arsenite stress...
2016: BMC Molecular Biology
https://www.readbyqxmd.com/read/27538368/reducing-translation-through-eif4g-ifg-1-improves-survival-under-er-stress-that-depends-on-heat-shock-factor-hsf-1-in-caenorhabditis-elegans
#15
Amber C Howard, Jarod Rollins, Santina Snow, Sarah Castor, Aric N Rogers
Although certain methods of lowering and/or altering mRNA translation are associated with increased lifespan, the mechanisms underlying this effect remain largely unknown. We previously showed that the increased lifespan conferred by reducing expression of eukaryotic translation initiation factor 4G (eIF4G/IFG-1) enhances survival under starvation conditions while shifting protein expression toward factors involved with maintaining ER-dependent protein and lipid balance. In this study, we investigated changes in ER homeostasis and found that lower eIF4G/IFG-1 increased survival under conditions of ER stress...
August 18, 2016: Aging Cell
https://www.readbyqxmd.com/read/27533468/synergistic-effects-of-eif4a-and-mek-inhibitors-on-proliferation-of-nras-mutant-melanoma-cell-lines
#16
Hélène Malka-Mahieu, Isabelle Girault, Margot Rubington, Melissa Leriche, Caroline Welsch, Nyam Kamsu-Kom, Qian Zhao, Laurent Desaubry, Stéphan Vagner, Caroline Robert
Activating mutations of the NRAS (neuroblastoma rat sarcoma viral oncogene) protein kinase, present in many cancers, induce a constitutive activation of both the RAS-RAF-MEK-ERK mitogen-activated protein kinase (MAPK) signal transduction pathway and the PI(3)K-AKT-mTOR, pathway. This in turn regulates the formation of the eIF4F eukaryotic translation initiation complex, comprising the eIF4E cap-binding protein, the eIF4G scaffolding protein and the eIF4A RNA helicase, which binds to the 7-methylguanylate cap (m(7)G) at the 5' end of messenger RNAs...
September 16, 2016: Cell Cycle
https://www.readbyqxmd.com/read/27525590/an-accurately-preorganized-ires-rna-structure-enables-eif4g-capture-for-initiation-of-viral-translation
#17
Shunsuke Imai, Parimal Kumar, Christopher U T Hellen, Victoria M D'Souza, Gerhard Wagner
Many viruses bypass canonical cap-dependent translation in host cells by using internal ribosomal entry sites (IRESs) in their transcripts; IRESs hijack initiation factors for the assembly of initiation complexes. However, it is currently unknown how IRES RNAs recognize initiation factors that have no endogenous RNA binding partners; in a prominent example, the IRES of encephalomyocarditis virus (EMCV) interacts with the HEAT-1 domain of eukaryotic initiation factor 4G (eIF4G). Here we report the solution structure of the J-K region of this IRES and show that its stems are precisely organized to position protein-recognition bulges...
September 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27501049/migration-and-epithelial-to-mesenchymal-transition-of-lung-cancer-can-be-targeted-via-translation-initiation-factors-eif4e-and-eif4gi
#18
Oshrat Attar-Schneider, Liat Drucker, Maya Gottfried
Metastasis underlies cancer morbidity and accounts for disease progression and significant death rates generally and in non-small cell lung cancer (NSCLC) particularly. Therefore, it is critically important to understand the molecular events that regulate metastasis. Accumulating data portray a central role for protein synthesis, particularly translation initiation (TI) factors eIF4E and eIF4G in tumorigenesis and patients' survival. We have published that eIF4E/eIF4GI activities and consequently NSCLC cell migration are modulated by bone-marrow mesenchymal stem cell secretomes, suggesting a role for TI in metastasis...
September 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27494274/coupling-between-the-dead-box-rna-helicases-ded1p-and-eif4a
#19
Zhaofeng Gao, Andrea A Putnam, Heath A Bowers, Ulf-Peter Guenther, Xuan Ye, Audrey Kindsfather, Angela K Hilliker, Eckhard Jankowsky
Eukaryotic translation initiation involves two conserved DEAD-box RNA helicases, eIF4A and Ded1p. Here we show that S. cerevisiae eIF4A and Ded1p directly interact with each other and simultaneously with the scaffolding protein eIF4G. We delineate a comprehensive thermodynamic framework for the interactions between Ded1p, eIF4A, eIF4G, RNA and ATP, which indicates that eIF4A, with and without eIF4G, acts as a modulator for activity and substrate preferences of Ded1p, which is the RNA remodeling unit in all complexes...
2016: ELife
https://www.readbyqxmd.com/read/27430620/amp-kinase-activation-alters-oxidant-induced-stress-granule-assembly-by-modulating-cell-signaling-and-microtubule-organization
#20
Hicham Mahboubi, Antonis E Koromilas, Ursula Stochaj
Eukaryotic cells assemble stress granules (SGs) when translation initiation is inhibited. Different cell signaling pathways regulate SG production. Particularly relevant to this process is 5'-AMP-activated protein kinase (AMPK), which functions as a stress sensor and is transiently activated by adverse physiologic conditions. Here, we dissected the role of AMPK for oxidant-induced SG formation. Our studies identified multiple steps of de novo SG assembly that are controlled by the kinase. Single-cell analyses demonstrated that pharmacological AMPK activation prior to stress exposure changed SG properties, because the granules became more abundant and smaller in size...
October 2016: Molecular Pharmacology
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