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https://www.readbyqxmd.com/read/28442428/rapamycin-modulation-of-p70-s6-kinase-signaling-inhibits-rift-valley-fever-virus-pathogenesis
#1
Todd M Bell, Virginia Espina, Svetlana Senina, Caitlin Woodson, Ashwini Brahms, Brian Carey, Shih-Chao Lin, Lindsay Lundberg, Chelsea Pinkham, Alan Baer, Claudius Mueller, Elizabeth A Chlipala, Faye Sharman, Cynthia de la Fuente, Lance Liotta, Kylene Kehn-Hall
Despite over 60 years of research on antiviral drugs, very few are FDA approved to treat acute viral infections. Rift Valley fever virus (RVFV), an arthropod borne virus that causes hemorrhagic fever in severe cases, currently lacks effective treatments. Existing as obligate intracellular parasites, viruses have evolved to manipulate host cell signaling pathways to meet their replication needs. Specifically, translation modulation is often necessary for viruses to establish infection in their host. Here we demonstrated phosphorylation of p70 S6 kinase, S6 ribosomal protein, and eIF4G following RVFV infection in vitro through western blot analysis and in a mouse model of infection through reverse phase protein microarrays (RPPA)...
April 22, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28428548/antiviral-activities-of-schizonepeta-tenuifolia-briq-against-enterovirus-71-in-vitro-and-in-vivo
#2
Sin-Guang Chen, Mei-Ling Cheng, Kuan-Hsing Chen, Jim-Tong Horng, Ching-Chuan Liu, Shih-Min Wang, Hiroaki Sakurai, Yann-Lii Leu, Shulhn-Der Wang, Hung-Yao Ho
No effective drug is currently available for treatment of enterovirus 71 (EV71) infection. Schizonepeta tenuifolia Briq. (ST) has been used as a herbal constituent of traditional Chinese medicine. We studied whether the aqueous extract of Schizonepeta tenuifolia Briq (STE) has antiviral activity. STE inhibited replication of EV71, as evident by its ability to diminish plaque formation and cytopathic effect induced by EV71, and to inhibit the synthesis of viral RNA and protein. Moreover, daily single-dose STE treatment significantly improved the survival of EV71-infected mice, and ameliorated the symptoms...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28287245/yela-a-putative-dictyostelium-translational-regulator-acts-as-antagonist-of-dif-1-signaling-to-control-cell-type-proportioning
#3
Yoko Yamada, Chris Sugden, Jeffrey G Williams
DIF-1 (differentiation-inducing factor1) is a polyketide produced by Dictyostelium prespore cells which induces initially uncommitted cells to differentiate as prestalk cells. Exposure of cells to DIF-1 causes transitory hypo-phosphorylation of seven serine residues in YelA, a protein with a region of strong homology to the MIF4G domain of the eukaryotic initiation factor eIF4G. Based upon its domain architecture, which in one important aspect closely resembles that of Death-Associated Protein 5 (DAP5), we predict a role in stimulating internal ribosome entry-driven mRNA translation...
2017: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/28287067/translational-control-of-mrnas-by-3-untranslated-region-binding-proteins
#4
Akio Yamashita, Osamu Takeuchi
Eukaryotic gene expression is precisely regulated at all points between transcription and translation. In this review, we focus on translational control mediated by the 3'-untranslated regions (UTRs) of mRNAs. mRNA 3'-UTRs contain cis-acting elements that function in the regulation of protein translation or mRNA decay. Each RNA binding protein that binds to these cis-acting elements regulates mRNA translation via various mechanisms targeting the mRNA cap structure, the eukaryotic initiation factor 4E (eIF4E)-eIF4G complex, ribosomes, and the poly (A) tail...
April 2017: BMB Reports
https://www.readbyqxmd.com/read/28244149/eukaryotic-translation-initiation-factor-2b-beta-eif2b%C3%AE-a-new-class-of-plant-virus-resistance-gene
#5
Shopan Jannat, Haipeng Mou, Lili Zhang, Changtong Zhang, Weiwei Ma, John A Walsh, Zhongyuan Hu, Jinghua Yang, Mingfang Zhang
Recessive resistances to plant viruses in the Potyvirus genus have been found to be based on mutations in the plant eukaryotic translation initiation factors, eIF4E and eIF4G or their isoforms. Here we report that natural, monogenic recessive resistance to the potyvirus Turnip mosaic virus (TuMV) has been found in a number of mustard (Brassica juncea) accessions. Bulked segregant analysis and sequencing of resistant and susceptible plant lines indicated the resistance is controlled by a single recessive gene, recessive TuMV resistance 03 (retr03), an allele of the eukaryotic translation initiation factor 2B-beta (eIF2Bβ)...
February 28, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28242763/eukaryotic-translation-initiation-factor-4g-eif4g-coordinates-interactions-with-eif4a-eif4b-and-eif4e-in-binding-and-translation-of-the-barley-yellow-dwarf-virus-3-cap-independent-translation-element-bte
#6
Pei Zhao, Qiao Liu, W Allen Miller, Dixie J Goss
Barley yellow dwarf virus RNA, lacking a 5' cap and a 3' poly(A) tail, contains a cap-independent translation element (BTE) in the 3'-untranslated region that interacts with host translation initiation factor eIF4G. To determine how eIF4G recruits the mRNA, three eIF4G deletion mutants were constructed: (i) eIF4G601-1196, containing amino acids 601-1196, including the putative BTE-binding region, and binding domains for eIF4E, eIF4A, and eIF4B; (ii) eIF4G601-1488, which contains an additional C-terminal eIF4A-binding domain; and (iii) eIF4G742-1196, which lacks the eIF4E-binding site...
April 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28199446/translational-control-in-plant-antiviral-immunity
#7
João Paulo B Machado, Iara P Calil, Anésia A Santos, Elizabeth P B Fontes
Due to the limited coding capacity of viral genomes, plant viruses depend extensively on the host cell machinery to support the viral life cycle and, thereby, interact with a large number of host proteins during infection. Within this context, as plant viruses do not harbor translation-required components, they have developed several strategies to subvert the host protein synthesis machinery to produce rapidly and efficiently the viral proteins. As a countermeasure against infection, plants have evolved defense mechanisms that impair viral infections...
February 13, 2017: Genetics and Molecular Biology
https://www.readbyqxmd.com/read/28179526/a-sequence-independent-unstructured-internal-ribosome-entry-site-is-responsible-for-internal-expression-of-the-coat-protein-of-turnip-crinkle-virus
#8
Jared May, Philip Johnson, Huma Saleem, Anne E Simon
To maximize the coding potential of viral genomes, internal ribosome entry sites (IRES) can be used to bypass the traditional requirement of a 5' cap and some/all of the associated translation initiation factors. Although viral IRES typically contain higher-order RNA structure, an unstructured sequence of about 84 nucleotides (nt) immediately upstream of the Turnip crinkle virus (TCV) coat protein (CP) open reading frame (ORF) has been found to promote internal expression of the CP from the genomic RNA (gRNA) both in vitro and in vivo An absence of extensive RNA structure was predicted using RNA folding algorithms and confirmed by selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) RNA structure probing...
April 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28131007/expression-of-the-cytoplasmic-nucleolin-for-post-transcriptional-regulation-of-macrophage-colony-stimulating-factor-mrna-in-ovarian-and-breast-cancer-cells
#9
Ho-Hyung Woo, Sang C Lee, Steven J Gibson, Setsuko K Chambers
The formation of the mRNP complex is a critical component of translational regulation and mRNA decay. Both the 5' and 3'UTRs of CSF-1 mRNA are involved in post-transcriptional regulation. In CSF-1 mRNA, a small hairpin loop structure is predicted to form at the extreme 5' end (2-21nt) of the 5'UTR. Nucleolin binds the hairpin loop structure in the 5'UTR of CSF-1 mRNA and enhances translation, while removal of this hairpin loop nucleolin binding element dramatically represses translation. Thus in CSF-1 mRNA, the hairpin loop nucleolin binding element is critical for translational regulation...
March 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28095120/the-bent-conformation-of-poly-a-binding-protein-induced-by-rna-binding-is-required-for-its-translational-activation-function
#10
Ka Young Hong, Seung Hwan Lee, Sohyun Gu, Eunah Kim, Sihyeon An, Junyoung Kwon, Jong-Bong Lee, Sung Key Jang
A recent study revealed that poly(A)-binding protein (PABP) bound to poly(A) RNA exhibits a sharply bent configuration at the linker region between RNA-recognition motif 2 (RRM2) and RRM3, whereas free PABP exhibits a highly flexible linear configuration. However, the physiological role of the bent structure of mRNA-bound PABP remains unknown. We investigated a role of the bent structure of PABP by constructing a PABP variant that fails to form the poly(A)-dependent bent structure but maintains its poly(A)-binding activity...
March 4, 2017: RNA Biology
https://www.readbyqxmd.com/read/28046134/the-triticum-mosaic-virus-5-leader-binds-to-both-eif4g-and-eifiso4g-for-translation
#11
Robyn Roberts, Laura K Mayberry, Karen S Browning, Aurélie M Rakotondrafara
We recently identified a remarkably strong (739 nt-long) IRES-like element in the 5' untranslated region (UTR) of Triticum mosaic virus (TriMV, Potyviridae). Here, we define the components of the cap-binding translation initiation complex that are required for TriMV translation. Using bio-layer interferometry and affinity capture of the native translation apparatus, we reveal that the viral translation element has a ten-fold greater affinity for the large subunit eIF4G/eIFiso4G than to the cap binding protein eIF4E/eIFiso4E...
2017: PloS One
https://www.readbyqxmd.com/read/27941351/anti-cancer-effect-of-cap-translation-inhibitor-4egi-1-in-human-glioma-u87-cells-involvement-of-mitochondrial-dysfunction-and-er-stress
#12
Ming Wu, Chi Zhang, Xue-Jun Li, Qing Liu, Siyi Wanggou
BACKGROUND: Cancer cells are frequently addicted to deregulated oncogenic protein translation that usually arises as a consequence of increased signaling flux from eIF4F activation. The small molecule 4EG-I, a potent inhibitor of translation initiation through disrupting eIF4E/eIF4G interaction, has been shown to exert anticancer effects in animal models of human cancers. METHODS: Here, we extensively investigated the anticancer activity of 4EGI-1 in human glioma U87 cells...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27928055/minimum-noise-production-of-translation-factor-eif4g-maps-to-a-mechanistically-determined-optimal-rate-control-window-for-protein-synthesis
#13
Xiang Meng, Helena Firczuk, Paola Pietroni, Richard Westbrook, Estelle Dacheux, Pedro Mendes, John E G McCarthy
Gene expression noise influences organism evolution and fitness. The mechanisms determining the relationship between stochasticity and the functional role of translation machinery components are critical to viability. eIF4G is an essential translation factor that exerts strong control over protein synthesis. We observe an asymmetric, approximately bell-shaped, relationship between the average intracellular abundance of eIF4G and rates of cell population growth and global mRNA translation, with peak rates occurring at normal physiological abundance...
January 25, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/27899360/widespread-and-dynamic-translational-control-of-red-blood-cell-development
#14
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. Our results uncover pervasive translational control of protein synthesis, with widespread alternative translation initiation and termination, robust discrimination of long noncoding from micropeptide-encoding RNAs, and dynamic use of upstream open reading frames. Further, we identify hundreds of messenger RNAs (mRNAs) whose translation efficiency is dynamically controlled during erythropoiesis and that enrich for target sites of RNA-binding proteins that are specific to hematopoietic cells, thus unraveling potential regulators of erythroid translational programs...
February 2, 2017: Blood
https://www.readbyqxmd.com/read/27858515/eif4b-stimulates-eif4a-atpase-and-unwinding-activities-by-direct-interaction-through-its-7-repeats-region
#15
Alexandra Zoi Andreou, Ulf Harms, Dagmar Klostermeier
Eukaryotic translation initiation starts with binding of the eIF4F complex to the 5'-m(7)G 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) toward 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...
January 2, 2017: RNA Biology
https://www.readbyqxmd.com/read/27833593/recessive-resistance-to-plant-viruses-potential-resistance-genes-beyond-translation-initiation-factors
#16
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
#17
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...
December 2016: RNA Biology
https://www.readbyqxmd.com/read/27773676/the-structures-of-eif4e-eif4g-complexes-reveal-an-extended-interface-to-regulate-translation-initiation
#18
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
#19
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
#20
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...
April 2017: Shock
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