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https://www.readbyqxmd.com/read/28062854/sf3b1-mutations-associated-with-myelodysplastic-syndromes-alter-the-fidelity-of-branchsite-selection-in-yeast
#1
Tucker J Carrocci, Douglas M Zoerner, Joshua C Paulson, Aaron A Hoskins
RNA and protein components of the spliceosome work together to identify the 5' splice site, the 3' splice site, and the branchsite (BS) of nascent pre-mRNA. SF3b1 plays a key role in recruiting the U2 snRNP to the BS. Mutations in human SF3b1 have been linked to many diseases such as myelodysplasia (MDS) and cancer. We have used SF3b1 mutations associated with MDS to interrogate the role of the yeast ortholog, Hsh155, in BS selection and splicing. These alleles change how the spliceosome recognizes the BS and alter splicing when nonconsensus nucleotides are present at the -2, -1 and +1 positions relative to the branchpoint adenosine...
January 6, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28059701/structural-and-biochemical-analyses-of-the-dead-box-atpase-sub2-in-association-with-tho-or-yra1
#2
Yi Ren, Philip Schmiege, Günter Blobel
mRNA is cotranscrptionally processed and packaged into messenger ribonucleoprotein particles (mRNPs) in the nucleus. Prior to export through the nuclear pore, mRNPs undergo several obligatory remodeling reactions. In yeast, one of these reactions involves loading of the mRNA-binding protein Yra1 by the DEAD-box ATPase Sub2 as assisted by the hetero-pentameric THO complex. To obtain molecular insights into reaction mechanisms, we determined crystal structures of two relevant complexes: a THO hetero-pentamer bound to Sub2 at 6...
January 6, 2017: ELife
https://www.readbyqxmd.com/read/28035044/a-role-for-gle1-a-regulator-of-dead-box-rna-helicases-at-centrosomes-and-basal-bodies
#3
Li-En Jao, Abdalla Akef, Susan R Wente
Control of organellar assembly and function is critical to eukaryotic homeostasis and survival. Gle1 is a highly conserved regulator of RNA-dependent DEAD-box ATPase proteins, with critical roles in both mRNA export and translation. In addition to its well-defined interaction with nuclear pore complexes, here we find that Gle1 is enriched at the centrosome and basal body. Gle1 assembles into the toroid-shaped pericentriolar material around the mother centriole. Reduced Gle1 levels are correlated with decreased pericentrin localization at the centrosome and microtubule organization defects...
January 1, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28030561/drosophila-ddx3-belle-exerts-its-function-outside-of-the-wnt-wingless-signaling-pathway
#4
Fabian H Jenny, Konrad Basler
The helicases human DDX3 and Drosophila Belle (Bel) are part of a well-defined subfamily of the DEAD-box helicases. Individual subfamily-members perform a myriad of functions in nuclear and cytosolic RNA metabolism. It has also been reported that DDX3X is involved in cell signaling, including IFN-α and IFN-β inducing pathways upon viral infection as well as in Wnt signaling. Here we used a collection of EMS-induced bel alleles recovered from a Wingless (Wg) suppressor screen to analyze the role of the Drosophila homolog of DDX3 in Wg/Wnt signaling...
2016: PloS One
https://www.readbyqxmd.com/read/27980081/ddx3-directly-regulates-traf3-ubiquitination-and-acts-as-a-scaffold-to-coordinate-assembly-of-signalling-complexes-downstream-of-mavs
#5
Lili Gu, Anthony Fullam, Niamh McCormack, Yvette Hoehn, Martina Schroeder
Human DEAD-box helicase 3 (DDX3) has been shown to contribute to type I interferon induction downstream of anti-viral pattern recognition receptors (PRRs). It binds to TANK-binding kinase 1 (TBK1) and IκB-kinase-ε (IKKε), the two key kinases mediating activation of Interferon regulatory factor (IRF) 3 and IRF7. We previously demonstrated that DDX3 facilitates IKKε activation downstream of RIG-I and then links the activated kinase to IRF3. In this study, we probed the interactions between DDX3 and other key signalling molecules in the RIG-I pathway and identified a novel direct interaction between DDX3 and TRAF3 mediated by a TRAF-interaction motif in the N-terminus of DDX3, which was required for TRAF3 ubiquitination...
December 15, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27965645/glucose-induces-ecf-sigma-factor-genes-sigx-and-sigm-independent-of-cognate-anti-sigma-factors-through-acetylation-of-csha-in-bacillus-subtilis
#6
Mitsuo Ogura, Kei Asai
Extracytoplasmic function (ECF) σ factors have roles related to cell envelope and/or cell membrane functions, in addition to other cellular functions. Without cell-surface stresses, ECF σ factors are sequestered by the cognate anti-σ factor, leading to inactivation and the resultant repression of regulons due to the inhibition of transcription of their own genes. Bacillus subtilis has seven ECF σ factors including σ(X) and σ(M) that transcribe their own structural genes. Here, we report that glucose addition to the medium induced sigX and sigM transcription independent of their anti-σ factors...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27941883/the-dead-box-protein-p68-a-novel-coactivator-of-stat3-in-mediating-oncogenesis
#7
M Sarkar, V Khare, M K Ghosh
DEAD box RNA helicase p68 acts as a transcriptional coactivator of several oncogenic transcription factors apart from being a vital player of RNA metabolism. Signal transducer and activator of transcription 3 (Stat3) is a major oncogenic contributor of diverse cancers, including that of colon. Deciphering the mechanistic insights of coactivation of Stat3 transcriptional activity may aid in improved therapeutic strategies. Here we report for the first time a novel mechanism of alliance between p68 and Stat3 in stimulating transcriptional activity of Stat3...
December 12, 2016: Oncogene
https://www.readbyqxmd.com/read/27940554/rna-helicase-ddx19-stabilizes-ribosomal-elongation-and-termination-complexes
#8
Tatiana Mikhailova, Ekaterina Shuvalova, Alexander Ivanov, Denis Susorov, Alexey Shuvalov, Peter M Kolosov, Elena Alkalaeva
The human DEAD-box RNA-helicase DDX19 functions in mRNA export through the nuclear pore complex. The yeast homolog of this protein, Dbp5, has been reported to participate in translation termination. Using a reconstituted mammalian in vitro translation system, we show that the human protein DDX19 is also important for translation termination. It is associated with the fraction of translating ribosomes. We show that DDX19 interacts with pre-termination complexes (preTCs) in a nucleotide-dependent manner. Furthermore, DDX19 increases the efficiency of termination complex (TC) formation and the peptide release in the presence of eukaryotic release factors...
December 9, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27864075/the-natural-compound-silvestrol-is-a-potent-inhibitor-of-ebola-virus-replication
#9
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...
January 2017: Antiviral Research
https://www.readbyqxmd.com/read/27858515/eif4b-stimulates-eif4a-atpase-and-unwinding-activities-by-direct-interaction-through-its-7-repeats-region
#10
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...
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
#11
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
#12
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 Díez
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...
January 2017: Genome Research
https://www.readbyqxmd.com/read/27821284/the-nucleolar-helicase-ddx56-redistributes-to-west-nile-virus-assembly-sites
#13
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
#14
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...
March 2017: Biopolymers
https://www.readbyqxmd.com/read/27811910/codon-optimality-and-mrna-decay
#15
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
#16
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-gene-is-required-for-chromosome-breakage-in-tetrahymena
#17
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 thermophile encodes two p68-like helicases, Drh1p and Lia2p. 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...
December 15, 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
#18
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
#19
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
#20
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
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