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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
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
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
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
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
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
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
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
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
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
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
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
Luqing Zhao, Yitao Mao, Yuelong Zhao, Yanong He
DDX3X, located on the X-chromosome, belongs to the DEAD-box RNA helicase family and acts as a key RNA-binding protein to exert its regulatory functions in various biological processes. In this paper, knock-down the expression of DDX3X can affect a subset of miRNA expression levels, especially for miR-1, miR-141, miR-145, miR-19b, miR-20a and miR-34a. Through adopting the immunoprecipitation (IP), RNA immunoprecipitation (RIP), dual luciferase reporter assays, we illustrate that DDX3X could interact with Drosha/DGCR8 complex, elevate the processing activity of Drosha/DGCR8 complex on pri-miRNAs, and increase mature miRNA expression levels...
2016: Scientific Reports
Peter D Nagy
Plant positive-strand (+)RNA viruses are intracellular infectious agents that reorganize subcellular membranes and rewire the cellular metabolism of host cells to achieve viral replication in elaborate replication compartments. This review describes the viral replication process based on tombusviruses, highlighting common strategies with other plant and animal viruses. Overall, the works on Tomato bushy stunt virus (TBSV) have revealed intriguing and complex functions of co-opted cellular translation factors, heat shock proteins, DEAD-box helicases, lipid transfer proteins, and membrane-deforming proteins in virus replication...
September 29, 2016: Annual Review of Virology
Mehrnoush Dehghani, Paul Lasko
The DEAD-box RNA helicase Vasa (Vas, also known as DDX4) is required for germ cell development. In Drosophila, analysis of hypomorphic mutations has implicated maternally expressed Vas in germ cell formation and posterior embryonic patterning. vas-null females, which rarely complete oogenesis, exhibit defects in mitotic progression of germline stem cells, Piwi-interacting RNA (piRNA)-mediated transposon silencing, and translation of Gurken (Grk), an EGFR ligand. The carboxy-terminal region of Vas orthologs throughout the animal kingdom consists of several acidic residues as well as an invariant tryptophan in the penultimate or ultimate position (Trp660 in Drosophila melanogaster)...
August 29, 2016: Development Genes and Evolution
Lei Li, Devon R Germain, Ho-Yin Poon, Matthew R Hildebrandt, Elizabeth A Monckton, Darin McDonald, Michael J Hendzel, Roseline Godbout
Although RNA and RNA binding proteins have been linked to double strand breaks (DSBs), little is known regarding their roles in the cellular response to DSBs and if any, in the repair process. Here, we provide direct evidence for the presence of RNA-DNA hybrids at DSBs and suggest that binding of RNA to DNA at DSBs may impact repair efficiency. Our data indicate that the RNA unwinding protein DEAD box 1 (DDX1) is required for efficient DSB repair and cell survival post IR, with depletion of DDX1 resulting in reduced DSB repair by homologous recombination (HR)...
August 22, 2016: Molecular and Cellular Biology
Younghoon Kim, Sua Myong
DEAD box RNA helicases play central roles in RNP biogenesis. We reported earlier that LAF-1, a DEAD box RNA helicase in C. elegans, dynamically interacts with RNA and that the interaction likely contributes to the fluidity of RNP droplets. Here we investigate the molecular basis of the interaction of RNA with LAF-1 and its human homolog, DDX3X. We show that both LAF-1 and DDX3X, at low concentrations, are monomers that induce tight compaction of single-stranded RNA. At high concentrations, the proteins are multimeric and dynamically interact with RNA in an RNA length-dependent manner...
September 1, 2016: Molecular Cell
Bin Lin, Feng Wang, Jiaxiang Wang, Chengyang Xu, Hui Zhao, Zhaoyun Cheng, Deguang Feng
p72 (probable ATP-dependent RNA helicase DDX17) belongs to the DEAD‑box RNA helicase family. p72 is important in RNA processing. Thus, the role of p72 in doxorubicin (DOX)‑induced cardiomyocyte injury was investigated in the present study. The changes in p72 expression levels were studied in cultured neonatal cardiomyocytes and p72 overexpression was induced using adenovirus vectors. To investigate the production of reactive oxygen species (ROS), dihydroethidium staining was conducted. TUNEL and Hoechst staining were used to indicate cell apoptosis...
October 2016: Molecular Medicine Reports
Yan Jiang, Yanping Zhu, Zhi-Jie Liu, Songying Ouyang
RNA helicases are involved in almost every aspect of RNA, from transcription to RNA decay. DExD/H-box helicases comprise the largest SF2 helicase superfamily, which are characterized by two conserved RecA-like domains. In recent years, an increasing number of unexpected functions of these proteins have been discovered. They play important roles not only in innate immune response but also in diseases like cancers and chronic hepatitis C. In this review, we summarize the recent literatures on one member of the SF2 superfamily, the DEAD-box protein DDX41...
August 9, 2016: Protein & Cell
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
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