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https://www.readbyqxmd.com/read/27864075/the-natural-compound-silvestrol-is-a-potent-inhibitor-of-ebola-virus-replication
#1
Nadine Biedenkopf, Kerstin Lange-Grünweller, Falk W Schulte, Aileen Weißer, Christin Müller, Dirk Becker, Stephan Becker, Roland K Hartmann, Arnold Grünweller
The DEAD-box RNA helicase eIF4A, which is part of the heterotrimeric translation initiation complex in eukaryotes, is an important novel drug target in cancer research because its helicase activity is required to unwind extended and highly structured 5'-UTRs of several proto-oncogenes. Silvestrol, a natural compound isolated from the plant Aglaia foveolata, is a highly efficient, non-toxic and specific inhibitor of eIF4A. Importantly, 5'-capped viral mRNAs often contain structured 5'-UTRs as well, which may suggest a dependence on eIF4A for their translation by the host protein synthesis machinery...
November 15, 2016: Antiviral Research
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/27835882/subsite-specific-association-of-dead-box-rna-helicase-ddx60-with-the-development-and-prognosis-of-oral-squamous-cell-carcinoma
#3
Ting-Ying Fu, Chao-Nan Wu, Huei-Cin Sie, Jiin-Tsuey Cheng, Yaoh-Shiang Lin, Huei-Han Liou, Yu-Kai Tseng, Chih-Wen Shu, Kuo-Wang Tsai, Leing-Ming Yen, Hui-Wen Tseng, Ching-Jiunn Tseng, Luo-Ping Ger, Pei-Feng Liu
The clinical significance and biological function of DEXD/H box helicase 60 (DDX60) in oral cancer remains unknown. Herein, we evaluated the association of DDX60 expression with tumorigenesis and the prognosis of oral squamous cell carcinoma (OSCC). DDX60 expression was examined by immunohistochemistry on tissue microarray slides of 494 OSCC patients, including 180 buccal mucosal SCC (BMSCC), 241 tongue SCC (TSCC), and 73 lip SCC (LSCC) patients. DDX60 expression was significantly increased in all three subsites of OSCC compared to its expression in tumor adjacent normal tissues...
November 8, 2016: Oncotarget
https://www.readbyqxmd.com/read/27821408/a-novel-translational-control-mechanism-involving-rna-structures-within-coding-sequences
#4
Jennifer Jungfleisch, Danny D Nedialkova, Ivan Dotu, Katherine E Sloan, Neus Martinez-Bosch, Lukas Brüning, Emanuele Raineri, Pilar Navarro, Markus T Bohnsack, Sebastian A Leidel, Juana Diez
The impact of RNA structures in coding sequences (CDS) within mRNAs is poorly understood. Here we identify a novel and highly conserved mechanism of translational control involving RNA structures within coding sequences and the DEAD-box helicase Dhh1. Using yeast genetics and genome-wide ribosome profiling analyses we show that this mechanism, initially derived from studies of the Brome Mosaic virus RNA genome, extends to yeast and human mRNAs highly enriched in membrane and secreted proteins. All Dhh1-dependent mRNAs, viral and cellular, share key common features...
November 7, 2016: Genome Research
https://www.readbyqxmd.com/read/27821284/the-nucleolar-helicase-ddx56-redistributes-to-west-nile-virus-assembly-sites
#5
Colleen R Reid, Tom C Hobman
Flaviviruses, including the human pathogen, West Nile virus (WNV), are known to co-opt many host factors for their replication and propagation. To this end, we previously reported that the nucleolar DEAD-box RNA helicase, DDX56, is important for production of infectious WNV virions. In this study, we show that WNV infection results in relocalization of DDX56 from nucleoli to virus assembly sites on the endoplasmic reticululm (ER), an observation that is consistent with a role for DDX56 in WNV virion assembly...
November 4, 2016: Virology
https://www.readbyqxmd.com/read/27813083/dbpa-is-a-region-specific-rna-helicase
#6
Anthony F T Moore, Riley C Gentry, Eda Koculi
DbpA is a DEAD-box RNA helicase implicated in RNA structural rearrangements in the peptidyl transferase center. DbpA contains an RNA binding domain, responsible for tight binding of DbpA to hairpin 92 of 23S ribosomal RNA, and a RecA-like catalytic core responsible for double-helix unwinding. It is not known if DbpA unwinds only the RNA helices that are part of a specific RNA structure, or if DbpA unwinds any RNA helices within the catalytic core's grasp. In other words, it is not known if DbpA is a site-specific enzyme or region-specific enzyme...
November 4, 2016: Biopolymers
https://www.readbyqxmd.com/read/27811910/codon-optimality-and-mrna-decay
#7
Yuriko Harigaya, Roy Parker
Recent evidence indicates that codon optimality is a broad determinant of mRNA stability. A study by Radhakrishnan et al. in Cell raises the possibility that the conserved DEAD-box protein Dhh1 underlies the phenomenon.
December 2016: Cell Research
https://www.readbyqxmd.com/read/27811006/retraction-of-molecular-cloning-and-characterization-of-a-salinity-stress-induced-gene-encoding-dead-box-helicase-from-the-halophyte-apocynum-venetum
#8
H H Liu, J Liu, S L Fan, M Z Song, X L Han, F Liu, F F Shen
No abstract text is available yet for this article.
November 3, 2016: Journal of Experimental Botany
https://www.readbyqxmd.com/read/27793833/drh1-a-p68-related-rna-helicase-is-required-for-chromosome-breakage-in-tetrahymena
#9
Stephen L McDaniel, Erica Zweifel, Peter K W Harris, Meng-Chao Yao, Eric S Cole, Douglas L Chalker
The p68 DEAD box helicases comprise a widely conserved protein family involved in a large range of biological processes including transcription, splicing, and translation. The genome of the ciliate Tetrahymena thermophila encodes two p68-like helicases, DRH1 and LIA2 We show that DRH1 is essential for growth and completion of development. In growing cells, Drh1p is excluded from the nucleus and accumulates near cortical basal bodies. In contrast, during sexual reproduction, this protein localizes to meiotic micronuclei, initially in punctate foci in regions where centromeres and telomeres are known to reside and later in post-zygotic differentiating somatic macronuclei...
October 28, 2016: Biology Open
https://www.readbyqxmd.com/read/27736973/the-dead-box-rna-helicase-ddx3-interacts-with-nf-%C3%AE%C2%BAb-subunit-p65-and-suppresses-p65-mediated-transcription
#10
Nian Xiang, Miao He, Musarat Ishaq, Yu Gao, Feifei Song, Liang Guo, Li Ma, Guihong Sun, Dan Liu, Deyin Guo, Yu Chen
RNA helicase family members exhibit diverse cellular functions, including in transcription, pre-mRNA processing, RNA decay, ribosome biogenesis, RNA export and translation. The RNA helicase DEAD-box family member DDX3 has been characterized as a tumour-associated factor and a transcriptional co-activator/regulator. Here, we demonstrate that DDX3 interacts with the nuclear factor (NF)-κB subunit p65 and suppresses NF-κB (p65/p50)-mediated transcriptional activity. The downregulation of DDX3 by RNA interference induces the upregulation of NF-κB (p65/p50)-mediated transcription...
2016: PloS One
https://www.readbyqxmd.com/read/27735940/ddx3-dead-box-rna-helicase-plays-a-central-role-in-mitochondrial-protein-quality-control-in-leishmania
#11
Prasad Kottayil Padmanabhan, Ouafa Zghidi-Abouzid, Mukesh Samant, Carole Dumas, Bruno Guedes Aguiar, Jerome Estaquier, Barbara Papadopoulou
DDX3 is a highly conserved member of ATP-dependent DEAD-box RNA helicases with multiple functions in RNA metabolism and cellular signaling. Here, we describe a novel function for DDX3 in regulating the mitochondrial stress response in the parasitic protozoan Leishmania. We show that genetic inactivation of DDX3 leads to the accumulation of mitochondrial reactive oxygen species (ROS) associated with a defect in hydrogen peroxide detoxification. Upon stress, ROS production is greatly enhanced, causing mitochondrial membrane potential loss, mitochondrial fragmentation, and cell death...
October 13, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27721487/structural-and-functional-analysis-of-ddx41-a-bispecific-immune-receptor-for-dna-and-cyclic-dinucleotide
#12
Hiroki Omura, Daisuke Oikawa, Takanori Nakane, Megumi Kato, Ryohei Ishii, Ryuichiro Ishitani, Fuminori Tokunaga, Osamu Nureki
In the innate immune system, pattern recognition receptors (PRRs) specifically recognize ligands derived from bacteria or viruses, to trigger the responsible downstream pathways. DEAD box protein 41 (DDX41) is an intracellular PRR that triggers the downstream pathway involving the adapter STING, the kinase TBK1, and the transcription factor IRF3, to activate the type I interferon response. DDX41 is unique in that it recognizes two different ligands; i.e., double-stranded DNA (dsDNA) and cyclic dinucleotides (CDN), via its DEAD domain...
October 10, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27708634/localization-of-components-of-the-rna-degrading-machine-in-bacillus-subtilis
#13
Nora Cascante-Estepa, Katrin Gunka, Jörg Stülke
In bacteria, the control of mRNA stability is crucial to allow rapid adaptation to changing conditions. In most bacteria, RNA degradation is catalyzed by the RNA degradosome, a protein complex composed of endo- and exoribonucleases, RNA helicases, and accessory proteins. In the Gram-positive model organism Bacillus subtilis, the existence of a RNA degradosome assembled around the membrane-bound endoribonuclease RNase Y has been proposed. Here, we have studied the intracellular localization of the protein that have been implicated in the potential B...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27704052/different-regulations-of-rom2-and-lrg1-expression-by-ccr4-pop2-and-dhh1-in-the-saccharomyces-cerevisiae-cell-wall-integrity-pathway
#14
Xia Li, Tetsuro Ohmori, Kaoru Irie, Yuichi Kimura, Yasuyuki Suda, Tomoaki Mizuno, Kenji Irie
Ccr4, a component of the Ccr4-Not cytoplasmic deadenylase complex, is known to be required for the cell wall integrity (CWI) pathway in the budding yeast Saccharomyces cerevisiae. However, it is not fully understood how Ccr4 and other components of the Ccr4-Not complex regulate the CWI pathway. Previously, we showed that Ccr4 functions in the CWI pathway together with Khd1 RNA binding protein. Ccr4 and Khd1 modulate a signal from Rho1 small GTPase in the CWI pathway by regulating the expression of ROM2 mRNA and LRG1 mRNA, encoding a guanine nucleotide exchange factor (GEF) and a GTPase-activating protein (GAP) for Rho1, respectively...
September 2016: MSphere
https://www.readbyqxmd.com/read/27697093/knockdown-of-ddx46-inhibits-the-invasion-and-tumorigenesis-in-osteosarcoma-cells
#15
Feng Jiang, Dengfeng Zhang, Guojun Li, Xiao Wang
DDX46, a member of the DEAD-box (DDX) helicase family, is involved in the development of several tumors. However, the exact role of DDX46 in osteosarcoma and the underlying mechanisms in tumorigenesis remain poorly understood. Thus, in the present study, we explored the role of DDX46 in osteosarcoma and the underlying mechanisms. Our results demonstrated that the expression levels of DDX46 in both mRNA and protein were greatly elevated in human osteosarcoma tissues and cell lines. Knockdown of DDX46 obviously inhibited osteosarcoma cell proliferation and tumor growth in vivo...
September 30, 2016: Oncology Research
https://www.readbyqxmd.com/read/27692063/atpase-activity-of-the-dead-box-protein-dhh1-controls-processing-body-formation
#16
Christopher Frederick Mugler, Maria Hondele, Stephanie Heinrich, Ruchika Sachdev, Pascal Vallotton, Adriana Y Koek, Leon Y Chan, Karsten Weis
Translational repression and mRNA degradation are critical mechanisms of posttranscriptional gene regulation that help cells respond to internal and external cues. In response to certain stress conditions, many mRNA decay factors are enriched in processing bodies (PBs), cellular structures involved in degradation and/or storage of mRNAs. Yet, how cells regulate assembly and disassembly of PBs remains poorly understood. Here, we show that in budding yeast, mutations in the DEAD-box ATPase Dhh1 that prevent ATP hydrolysis, or that affect the interaction between Dhh1 and Not1, the central scaffold of the CCR4-NOT complex and an activator of the Dhh1 ATPase, prevent PB disassembly in vivo...
October 3, 2016: ELife
https://www.readbyqxmd.com/read/27687868/smc4-which-is-essentially-involved-in-lung-development-is-associated-with-lung-adenocarcinoma-progression
#17
Chengli Zhang, Manchao Kuang, Meng Li, Lin Feng, Kaitai Zhang, Shujun Cheng
Structural maintenance of chromosome 4 (SMC4) is a core subunit of condensin complexes that mainly contributes to chromosome condensation and segregation. Our previous study demonstrated that the gene expression profile during lung development is of great values for the study of lung cancer. In this study, we identified SMC4 through co-expression network analysis and clique percolation clustering using genes that constant changes during four stages of lung development. Gene ontology and KEGG pathway enrichment analysis demonstrated that SMC4 is closely related to cell cycle, cell adhesion, and RNA processing in lung development and carcinogenesis...
September 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27679741/ddx6-transfers-p-tefb-kinase-to-the-af4-af4n-aff1-super-elongation-complex
#18
Fabian Mück, Silvia Bracharz, Rolf Marschalek
AF4/AFF1 and AF5/AFF4 are both backbones for the assembly of "super elongation complexes" (SECs) that exert 2 distinct functions after the recruitment of P-TEFb from the 7SK snRNP: (1) initiation and elongation of RNA polymerase II gene transcription, and (2) modification of transcribed gene regions by distinct histone methylation patterns. In this study we aimed to investigate one of the initial steps, namely how P-TEFb is transferred from 7SK snRNPs to the SECs. In particular, we were interested in the role of DDX6 that we have recently identified as part of the AF4 complex...
2016: American Journal of Blood Research
https://www.readbyqxmd.com/read/27649531/mechanistic-insights-into-the-antilithiatic-proteins-from-terminalia-arjuna-a-proteomic-approach-in-urolithiasis
#19
Amisha Mittal, Simran Tandon, Surender Kumar Singla, Chanderdeep Tandon
Kidney stone formation during hyperoxaluric condition is inherently dependent on the interaction between renal epithelial cells and calcium oxalate (CaOx) crystals. Although modern medicine has progressed in terms of removal of these stones, recurrence and persistent side effects restricts their use. Strategies involving plant based agents which could be used as adjunct therapy is an area which needs to be explored. Plant proteins having antilithiatic activity is a hitherto unexplored area and therefore, we conducted a detailed identification and characterization of antilithiatic proteins from Terminalia arjuna (T...
2016: PloS One
https://www.readbyqxmd.com/read/27641505/the-dead-box-protein-dhh1p-couples-mrna-decay-and-translation-by-monitoring-codon-optimality
#20
Aditya Radhakrishnan, Ying-Hsin Chen, Sophie Martin, Najwa Alhusaini, Rachel Green, Jeff Coller
A major determinant of mRNA half-life is the codon-dependent rate of translational elongation. How the processes of translational elongation and mRNA decay communicate is unclear. Here, we establish that the DEAD-box protein Dhh1p is a sensor of codon optimality that targets an mRNA for decay. First, we find mRNAs whose translation elongation rate is slowed by inclusion of non-optimal codons are specifically degraded in a Dhh1p-dependent manner. Biochemical experiments show Dhh1p is preferentially associated with mRNAs with suboptimal codon choice...
September 22, 2016: Cell
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