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https://www.readbyqxmd.com/read/29150525/distinct-rna-unwinding-mechanisms-of-dead-box-and-deah-box-rna-helicase-proteins-in-remodeling-structured-rnas-and-rnps
#1
REVIEW
Benjamin Gilman, Pilar Tijerina, Rick Russell
Structured RNAs and RNA-protein complexes (RNPs) fold through complex pathways that are replete with misfolded traps, and many RNAs and RNPs undergo extensive conformational changes during their functional cycles. These folding steps and conformational transitions are frequently promoted by RNA chaperone proteins, notably by superfamily 2 (SF2) RNA helicase proteins. The two largest families of SF2 helicases, DEAD-box and DEAH-box proteins, share evolutionarily conserved helicase cores, but unwind RNA helices through distinct mechanisms...
November 17, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/29146961/identification-of-host-dead-box-rna-helicases-that-regulate-cellular-tropism-of-oncolytic-myxoma-virus-in-human-cancer-cells
#2
Masmudur M Rahman, Eugenie Bagdassarian, Mohamed A M Ali, Grant McFadden
Myxoma virus (MYXV), a Leporipoxvirus, is being developed as an oncolytic virotherapeutic for the treatment of a variety of human cancers. MYXV tropism for human cancer cells is largely mediated by intracellular signaling networks that regulate viral replication or innate antiviral response pathways. Thus, MYXV is fully or partially permissive for the majority of human cancer cells that harbor defects in antiviral signaling, but a minority are nonpermissive because the virus infection aborts before its completion...
November 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29138350/the-dead-box-rna-helicase-rh50-is-a-23s-4-5s-rrna-maturation-factor-that-functionally-overlaps-with-the-plastid-signaling-factor-gun1
#3
Francesca Paieri, Luca Tadini, Nikolay Manavski, Tatjana Kleine, Roberto Ferrari, Pietro Angelo Morandini, Paolo Pesaresi, Jörg Meurer, Dario Leister
DEAD-box RNA helicases (DBRHs) modulate RNA secondary structure, allowing RNA molecules to adopt the conformations required for interaction with their target proteins. RH50 is a chloroplast-located DBRH that co-localizes and is co-expressed with GUN1, a central factor in chloroplast-to-nucleus signaling. When combined with mutations that impair plastid gene expression (prors1-1, prpl11-1, prps1-1, prps21-1, prps17-1 and prpl24-1), rh50 and gun1 mutations evoke similar patterns of epistatic effects. These observations, together with the synergistic growth phenotype of the double mutant rh50-1 gun1-102, suggest that RH50 and GUN1 are functionally related and that this function is associated with plastid gene expression, in particular ribosome functioning...
November 14, 2017: Plant Physiology
https://www.readbyqxmd.com/read/29136196/analysis-of-the-natively-unstructured-rna-protein-recognition-core-in-the-escherichia-coli-rna-degradosome-and-its-interactions-with-regulatory-rna-hfq-complexes
#4
Heather A Bruce, Dijun Du, Dijana Matak-Vinkovic, Katarzyna J Bandyra, R William Broadhurst, Esther Martin, Frank Sobott, Alexander V Shkumatov, Ben F Luisi
The RNA degradosome is a multi-enzyme assembly that plays a central role in the RNA metabolism of Escherichia coli and numerous other bacterial species including pathogens. At the core of the assembly is the endoribonuclease RNase E, one of the largest E. coli proteins and also one that bears the greatest region predicted to be natively unstructured. This extensive unstructured region, situated in the C-terminal half of RNase E, is punctuated with conserved short linear motifs that recruit partner proteins, direct RNA interactions, and enable association with the cytoplasmic membrane...
November 9, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29127725/a-loss-of-function-homozygous-mutation-in-ddx59-implicates-a-conserved-dead-box-rna-helicase-in-nervous-system-development-and-function
#5
Vincenzo Salpietro, Stephanie Efthymiou, Andreea Manole, Bhawana Maurya, Sarah Wiethoff, Balasubramaniem Ashokkumar, Maria Concetta Cutrupi, Valeria Dipasquale, Sara Manti, Juan A Botia, Mina Ryten, Jana Vandrovcova, Oscar D Bello, Conceicao Bettencourt, Kshitij Mankad, Ashim Mukherjee, Mousumi Mutsuddi, Henry Houlden
We report on a homozygous frameshift deletion in DDX59 (c.185del: p.Phe62fs*13) in a family presenting with oro-facio-digital syndrome phenotype associated to a broad neurological involvement characterized by microcephaly, intellectual disability, epilepsy, and white matter signal abnormalities associated with cortical and sub-cortical ischemic events. DDX59 encodes a DEAD-box RNA helicase and its role in brain function and neurological diseases is unclear. We showed a reduction of mutant cDNA and perturbation of SHH signalling from patient-derived cell lines; furthermore, analysis of human brain gene expression provides evidence that DDX59 is enriched in oligodendrocytes and might act within pathways of leukoencephalopathies associated genes...
November 11, 2017: Human Mutation
https://www.readbyqxmd.com/read/29107644/the-glycolytic-pyruvate-kinase-is-recruited-directly-into-the-viral-replicase-complex-to-generate-atp-for-rna-synthesis
#6
Chingkai Chuang, K Reddisiva Prasanth, Peter D Nagy
Viruses accomplish their replication by exploiting many cellular resources, including metabolites and energy. Similarly to other (+)RNA viruses, tomato bushy stunt virus (TBSV) induces major changes in infected cells. However, the source of energy required to fuel TBSV replication is unknown. We find that TBSV co-opts the cellular glycolytic ATP-generating pyruvate kinase (PK) directly into the viral replicase complex to boost progeny RNA synthesis. The co-opted PK generates high levels of ATP within the viral replication compartment at the expense of a reduction in cytosolic ATP pools...
November 8, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/29037760/biochemical-differences-and-similarities-between-the-dead-box-helicase-orthologs-ddx3x-and-ded1p
#7
Deepak Sharma, Andrea A Putnam, Eckhard Jankowsky
DDX3X is a conserved DEAD-box RNA helicase involved in translation initiation and other processes of RNA metabolism. Mutations in human DDX3X and deregulation of its expression are linked to tumorigenesis and intellectual disability. The protein is also targeted by diverse viruses. Previous studies demonstrated helicase and NTPase activities for DDX3X, but important biochemical features of the enzyme remain unclear. Here, we systematically characterize enzymatic activities of human DDX3X and compare these to its closely related Saccharomyces cerevisiae ortholog Ded1p...
November 24, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28964860/fish-ddx3x-exerts-antiviral-function-against-grouper-nervous-necrosis-virus-infection
#8
Jiaxin Liu, Xiaohong Huang, Yepin Yu, Jingcheng Zhang, Songwei Ni, Yin Hu, Youhua Huang, Qiwei Qin
Human DEAD box ATP-dependent RNA helicase DDX3X has been demonstrated to exert crucial functions in carcinogenesis and antiviral immune response. However, to our knowledge, few information focused on the functions of fish DDX3X. In this study, we cloned and characterized a DDX3X homolog from orange spotted grouper (Epinephelus coioides) (EcDDX3X). EcDDX3X encoded a 733-amino acid protein which shared 97% and 76% identity to spiny damselfish (Acanthochromis polyacanthus) and human (Homo sapiens), respectively...
September 28, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28922368/a-tree-of-life-based-on-ninety-eight-expressed-genes-conserved-across-diverse-eukaryotic-species
#9
Pawan Kumar Jayaswal, Vivek Dogra, Asheesh Shanker, Tilak Raj Sharma, Nagendra Kumar Singh
Rapid advances in DNA sequencing technologies have resulted in the accumulation of large data sets in the public domain, facilitating comparative studies to provide novel insights into the evolution of life. Phylogenetic studies across the eukaryotic taxa have been reported but on the basis of a limited number of genes. Here we present a genome-wide analysis across different plant, fungal, protist, and animal species, with reference to the 36,002 expressed genes of the rice genome. Our analysis revealed 9831 genes unique to rice and 98 genes conserved across all 49 eukaryotic species analysed...
2017: PloS One
https://www.readbyqxmd.com/read/28869701/nup42-and-ip6-coordinate-gle1-stimulation-of-dbp5-ddx19b-for-mrna-export-in-yeast-and-human-cells
#10
Rebecca L Adams, Aaron C Mason, Laura Glass, Aditi, Susan R Wente
The mRNA lifecycle is driven through spatiotemporal changes in the protein composition of mRNA particles (mRNPs) that are triggered by RNA-dependent DEAD-box protein (Dbp) ATPases. As mRNPs exit the nuclear pore complex (NPC) in Saccharomyces cerevisiae, this remodeling occurs through activation of Dbp5 by inositol hexakisphosphate (IP6 )-bound Gle1. At the NPC, Gle1 also binds Nup42, but Nup42's molecular function is unclear. Here we employ the power of structure-function analysis in S. cerevisiae and human (h) cells, and find that the high-affinity Nup42-Gle1 interaction is integral to Dbp5 (hDDX19B) activation and efficient mRNA export...
December 2017: Traffic
https://www.readbyqxmd.com/read/28869602/targeting-mitochondrial-translation-by-inhibiting-ddx3-a-novel-radiosensitization-strategy-for-cancer-treatment
#11
M R Heerma van Voss, F Vesuna, G M Bol, J Afzal, S Tantravedi, Y Bergman, K Kammers, M Lehar, R Malek, M Ballew, N Ter Hoeve, D Abou, D Thorek, C Berlinicke, M Yazdankhah, D Sinha, A Le, R Abrahams, P T Tran, P J van Diest, V Raman
DDX3 is a DEAD box RNA helicase with oncogenic properties. RK-33 is developed as a small-molecule inhibitor of DDX3 and showed potent radiosensitizing activity in preclinical tumor models. This study aimed to assess DDX3 as a target in breast cancer and to elucidate how RK-33 exerts its anti-neoplastic effects. High DDX3 expression was present in 35% of breast cancer patient samples and correlated with markers of aggressiveness and shorter survival. With a quantitative proteomics approach, we identified proteins involved in the mitochondrial translation and respiratory electron transport pathways to be significantly downregulated after RK-33 or DDX3 knockdown...
September 4, 2017: Oncogene
https://www.readbyqxmd.com/read/28846086/the-rna-helicase-ddx46-inhibits-innate-immunity-by-entrapping-m-6-a-demethylated-antiviral-transcripts-in-the-nucleus
#12
Qingliang Zheng, Jin Hou, Ye Zhou, Zhenyang Li, Xuetao Cao
DEAD-box (DDX) helicases are vital for the recognition of RNA and metabolism and are critical for the initiation of antiviral innate immunity. Modification of RNA is involved in many biological processes; however, its role in antiviral innate immunity has remained unclear. Here we found that nuclear DDX member DDX46 inhibited the production of type I interferons after viral infection. DDX46 bound Mavs, Traf3 and Traf6 transcripts (which encode signaling molecules involved in antiviral responses) via their conserved CCGGUU element...
October 2017: Nature Immunology
https://www.readbyqxmd.com/read/28842848/dead-box-helicase-6-ddx6-is-a-new-negative-regulator-for-milk-synthesis-and-proliferation-of-bovine-mammary-epithelial-cells
#13
Zhen Zhen, Minghui Zhang, Xiaohan Yuan, Bo Qu, Yanbo Yu, Xuejun Gao, Youwen Qiu
Milk synthesis of bovine mammary gland is a complex biological process that is regulated by hormones and nutrients, but the mechanism of these regulations still needs further research. DEAD-box helicase 6 (DDX6) is an important member of the RNA helicase family, involved in the regulation of mRNA storage and translation in different systems, but its physiological role and mechanism are largely unclear. In this study, we describe DDX6 as a potentially novel negative regulator for milk synthesis and proliferation of bovine mammary epithelial cells (BMECs)...
August 25, 2017: In Vitro Cellular & Developmental Biology. Animal
https://www.readbyqxmd.com/read/28842590/ddx3-localizes-to-the-centrosome-and-prevents-multipolar-mitosis-by-epigenetically-and-translationally-modulating-p53-expression
#14
Wei-Ju Chen, Wei-Ting Wang, Tsung-Yuan Tsai, Hao-Kang Li, Yan-Hwa Wu Lee
The DEAD-box RNA helicase DDX3 plays divergent roles in tumorigenesis, however, its function in mitosis is unclear. Immunofluorescence indicated that DDX3 localized to centrosome throughout the cell cycle and colocalized with centrosome-associated p53 during mitosis in HCT116 and U2OS cells. DDX3 depletion promoted chromosome misalignment, segregation defects and multipolar mitosis, eventually leading to G2/M delay and cell death. DDX3 prevented multipolar mitosis by inactivation and coalescence of supernumerary centrosomes...
August 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819113/insights-into-the-role-of-endonuclease-v-in-rna-metabolism-in-trypanosoma-brucei
#15
Daniel García-Caballero, Guiomar Pérez-Moreno, Antonio M Estévez, Luis Miguel Ruíz-Pérez, Antonio E Vidal, Dolores González-Pacanowska
Inosine may arise in DNA as a result of oxidative deamination of adenine or misincorporation of deoxyinosine triphosphate during replication. On the other hand, the occurrence of inosine in RNA is considered a normal and essential modification induced by specific adenosine deaminases acting on mRNA and tRNA. In prokaryotes, endonuclease V (EndoV) can recognize and cleave inosine-containing DNA. In contrast, mammalian EndoVs preferentially cleave inosine-containing RNA, suggesting a role in RNA metabolism for the eukaryotic members of this protein family...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28807014/epigenetic-reprogramming-converts-human-wharton-s-jelly-mesenchymal-stem-cells-into-functional-cardiomyocytes-by-differential-regulation-of-wnt-mediators
#16
G Bhuvanalakshmi, Frank Arfuso, Alan Prem Kumar, Arun Dharmarajan, Sudha Warrier
BACKGROUND: Lineage commitment of mesenchymal stem cells (MSCs) to cardiac differentiation is controlled by transcription factors that are regulated by epigenetic events, mainly histone deacetylation and promoter DNA methylation. Here, we studied the differentiation of human Wharton's jelly MSCs (WJMSCs) into the cardiomyocyte lineage via epigenetic manipulations. METHODS: We introduced these changes using inhibitors of DNA methyl transferase and histone deacetylase, DC301, DC302, and DC303, in various combinations...
August 14, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28790157/sirt7-and-the-dead-box-helicase-ddx21-cooperate-to-resolve-genomic-r-loops-and-safeguard-genome-stability
#17
Chenlin Song, Agnes Hotz-Wagenblatt, Renate Voit, Ingrid Grummt
R loops are three-stranded nucleic acid structures consisting of an RNA:DNA heteroduplex and a "looped-out" nontemplate strand. As aberrant formation and persistence of R loops block transcription elongation and cause DNA damage, mechanisms that resolve R loops are essential for genome stability. Here we show that the DEAD (Asp-Glu-Ala-Asp)-box RNA helicase DDX21 efficiently unwinds R loops and that depletion of DDX21 leads to accumulation of cellular R loops and DNA damage. Significantly, the activity of DDX21 is regulated by acetylation...
August 8, 2017: Genes & Development
https://www.readbyqxmd.com/read/28761359/nuclear-ddx3-expression-predicts-poor-outcome-in-colorectal-and-breast-cancer
#18
Marise R Heerma van Voss, Farhad Vesuna, Guus M Bol, Jan Meeldijk, Ana Raman, G Johan Offerhaus, Horst Buerger, Arvind H Patel, Elsken van der Wall, Paul J van Diest, Venu Raman
PURPOSE: DEAD box protein 3 (DDX3) is an RNA helicase with oncogenic properties that shuttles between the cytoplasm and nucleus. The majority of DDX3 is found in the cytoplasm, but a subset of tumors has distinct nuclear DDX3 localization of yet unknown biological significance. This study aimed to evaluate the significance of and mechanisms behind nuclear DDX3 expression in colorectal and breast cancer. METHODS: Expression of nuclear DDX3 and the nuclear exporter chromosome region maintenance 1 (CRM1) was evaluated by immunohistochemistry in 304 colorectal and 292 breast cancer patient samples...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28757063/atp-competitive-marine-derived-natural-products-that-target-the-dead-box-helicase-eif4a
#19
Joseph Tillotson, Magdalena Kedzior, Larissa Guimarães, Alison B Ross, Tara L Peters, Andrew J Ambrose, Cody J Schmidlin, Donna D Zhang, Letícia V Costa-Lotufo, Abimael D Rodríguez, Jonathan H Schatz, Eli Chapman
Activation of translation initiation is a common trait of cancer cells. Formation of the heterotrimeric eukaryotic initiation factor F (eIF4F) complex is the rate-limiting step in 5' m7GpppN cap-dependent translation. This trimeric complex includes the eIF4E cap binding protein, the eIF4G scaffolding protein, and the DEAD box RNA helicase eIF4A. eIF4A is an ATP-dependent helicase and because it is the only enzyme in the eIF4F complex, it has been shown to be a potential therapeutic target for a variety of malignancies...
September 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28746868/ddx6-represses-aberrant-activation-of-interferon-stimulated-genes
#20
Jennifer H Lumb, Qin Li, Lauren M Popov, Siyuan Ding, Marie T Keith, Bryan D Merrill, Harry B Greenberg, Jin Billy Li, Jan E Carette
The innate immune system tightly regulates activation of interferon-stimulated genes (ISGs) to avoid inappropriate expression. Pathological ISG activation resulting from aberrant nucleic acid metabolism has been implicated in autoimmune disease; however, the mechanisms governing ISG suppression are unknown. Through a genome-wide genetic screen, we identified DEAD-box helicase 6 (DDX6) as a suppressor of ISGs. Genetic ablation of DDX6 induced global upregulation of ISGs and other immune genes. ISG upregulation proved cell intrinsic, imposing an antiviral state and making cells refractory to divergent families of RNA viruses...
July 25, 2017: Cell Reports
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