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Rna helicase

Jacob O Brunkard, Tessa M Burch-Smith
Plastids are critical organelles in plant cells that perform diverse functions and are central to many metabolic pathways. Beyond their major roles in primary metabolism, of which their role in photosynthesis is perhaps best known, plastids contribute to the biosynthesis of phytohormones and other secondary metabolites, store critical biomolecules, and sense a range of environmental stresses. Accordingly, plastid-derived signals coordinate a host of physiological and developmental processes, often by emitting signalling molecules that regulate the expression of nuclear genes...
March 21, 2018: Essays in Biochemistry
Christina Pfaff, Hans F Ehrnsberger, Maria Flores-Tornero, Brian B Soerensen, Thomas Schubert, Gernot Längst, Joachim Griesenbeck, Stefanie Sprunck, Marion Grasser, Klaus D Grasser
The regulated transport of mRNAs from the cell nucleus to the cytosol is a critical step linking transcript synthesis and processing with translation. However, in plants, only few of the factors that act in the mRNA export pathway have been functionally characterised. Flowering plant genomes encode several members of the ALY protein family, which function as mRNA export factors in other organisms. Arabidopsis thaliana ALY1-4 are commonly detected in root and leaf cells, but are differentially expressed in reproductive tissue...
March 14, 2018: Plant Physiology
Luděk Eyer, Radim Nencka, Erik de Clercq, Katherine Seley-Radtke, Daniel Růžek
Nucleoside analogs represent the largest class of small molecule-based antivirals, which currently form the backbone of chemotherapy of chronic infections caused by HIV, hepatitis B or C viruses, and herpes viruses. High antiviral potency and favorable pharmacokinetics parameters make some nucleoside analogs suitable also for the treatment of acute infections caused by other medically important RNA and DNA viruses. This review summarizes available information on antiviral research of nucleoside analogs against arthropod-borne members of the genus Flavivirus within the family Flaviviridae, being primarily focused on description of nucleoside inhibitors of flaviviral RNA-dependent RNA polymerase, methyltransferase, and helicase/NTPase...
January 2018: Antiviral Chemistry & Chemotherapy
Isabelle Raymond-Bouchard, Jacqueline Goordial, Yevgen Zolotarov, Jennifer Ronholm, Martina Stromvik, Corien Bakermans, Lyle G Whyte
Permafrost accounts for 27% of all soil ecosystems and harbors diverse microbial communities. Our understanding of microorganisms in permafrost, their activities and adaptations, remains limited. Using five subzero-growing (cryophilic) permafrost bacteria, we examined features of cold adaptation through comparative genomic analyses with mesophilic relatives. The cryophiles possess genes associated with cold adaptation, including cold shock proteins, RNA helicases, and oxidative stress and carotenoid synthesis enzymes...
March 8, 2018: FEMS Microbiology Ecology
Frank Curmi, Ruben J Cauchi
Gemin3, also known as DDX20 or DP103, is a DEAD-box RNA helicase which is involved in more than one cellular process. Though RNA unwinding has been determined in vitro , it is surprisingly not required for all of its activities in cellular metabolism. Gemin3 is an essential gene, present in Amoeba and Metazoa. The highly conserved N-terminus hosts the helicase core, formed of the helicase- and DEAD-domains, which, based on crystal structure determination, have key roles in RNA binding. The C-terminus of Gemin3 is highly divergent between species and serves as the interaction site for several accessory factors that could recruit Gemin3 to its target substrates and/or modulate its function...
March 9, 2018: Biochemical Society Transactions
Wenting Zhao, Zhen Wang, Zewei Sun, Yuxian He, Dongdong Jian, Xiaotong Hu, Wang Zhang, Liangrong Zheng
The DEAD box protein DDX5, an ATP-dependent RNA helicase, plays an important role in transcriptional regulation and is associated with solid tumors and leukemia. However, its role in oxLDL-induced lipid uptake in macrophages remains unclear. In this study, we detected the expression of DDX5 mRNA and protein in oxidized low-density lipoprotein (oxLDL)-treated human primary macrophages that were induced from monocytes isolated from human peripheral blood with or without several chemical inhibitors using quantitative real-time PCR (qRT-PCR) or Western blotting...
March 6, 2018: Experimental Cell Research
Jan Michael Schuller, Sebastian Falk, Lisa Fromm, Ed Hurt, Elena Conti
The RNA exosome complex processes and degrades a wide range of transcripts, including ribosomal RNAs. We used cryo-EM to visualize the yeast nuclear exosome holo-complex captured on a precursor large ribosomal subunit (pre-60S) during 7S-to-5.8S rRNA processing. The cofactors of the nuclear exosome are sandwiched between the ribonuclease core complex (Exo-10) and the remodeled "foot" structure of the pre-60S particle, which harbors the 5.8S rRNA precursor. The exosome-associated helicase Mtr4 recognizes the preribosomal substrate by docking to specific sites on the 25S rRNA, captures the 3' extension of the 5...
March 8, 2018: Science
Marina Toompuu, Tea Tuomela, Pia Laine, Lars Paulin, Eric Dufour, Howard T Jacobs
RNA 3' polyadenylation is known to serve diverse purposes in biology, in particular, regulating mRNA stability and translation. Here we determined that, upon exposure to high levels of the intercalating agent ethidium bromide (EtBr), greater than those required to suppress mitochondrial transcription, mitochondrial tRNAs in human cells became polyadenylated. Relaxation of the inducing stress led to rapid turnover of the polyadenylated tRNAs. The extent, kinetics and duration of tRNA polyadenylation were EtBr dose-dependent, with mitochondrial tRNAs differentially sensitive to the stress...
March 6, 2018: Nucleic Acids Research
Alexis H Bennett, Marie-Francoise O'Donohue, Stacey R Gundry, Aye T Chan, Jeffrey Widrick, Isabelle Draper, Anirban Chakraborty, Yi Zhou, Leonard I Zon, Pierre-Emmanuel Gleizes, Alan H Beggs, Vandana A Gupta
Gene expression in a tissue-specific context depends on the combined efforts of epigenetic, transcriptional and post-transcriptional processes that lead to the production of specific proteins that are important determinants of cellular identity. Ribosomes are a central component of the protein biosynthesis machinery in cells; however, their regulatory roles in the translational control of gene expression in skeletal muscle remain to be defined. In a genetic screen to identify critical regulators of myogenesis, we identified a DEAD-Box RNA helicase, DDX27, that is required for skeletal muscle growth and regeneration...
March 2018: PLoS Genetics
Macarena Guijo, María Ceballos-Chávez, Elena Gómez-Marín, Laura Basurto-Cayuela, José C Reyes
Tudor domain containing protein 9 (TDRD9) is a RNA helicase normally expressed in the germline, where it is involved in the biosynthesis of PIWI-interacting RNAs (piRNAs). Here, we show that TDRD9 is highly expressed in a subset of non-small cell lung carcinomas and derived cell lines by hypomethylation of its CpG island. Furthermore, TDRD9 expression is associated with poor prognosis in lung adenocarcinoma. We find that downregulation of TDRD9 expression in TDRD9-positive cell lines causes a decrease in cell proliferation, S-phase cell cycle arrest, and apoptosis...
February 9, 2018: Oncotarget
Meriem Bekliz, Said Azza, Hervé Seligmann, Philippe Decloquement, Didier Raoult, Bernard La Scola
Acanthamoeba polyphaga mimivirus is the first giant virus ever described, with a 1.2-Mb genome which encodes 979 proteins including central components of the translation apparatus. One of these proteins, R458, was predicted to initiate translation, although its specific role remains unknown.We silenced the R458 gene using siRNA and compared viral fitness and protein expression in silenced versus wild-type mimivirus. Silencing decreased growth rate but viral particle production at the end of the viral cycle was unaffected...
March 7, 2018: Journal of Virology
Mandy Juarez, Alejandro Schcolnik-Cabrera, Alfonso Dueñas-Gonzalez
Drug repositioning is a highly studied alternative strategy to discover and develop anticancer drugs. This drug development approach identifies new indications for existing compounds. Ivermectin belongs to the group of avermectins (AVM), a series of 16-membered macrocyclic lactone compounds discovered in 1967, and FDA-approved for human use in 1987. It has been used by millions of people around the world exhibiting a wide margin of clinical safety. In this review, we summarize the in vitro and in vivo evidences demonstrating that ivermectin exerts antitumor effects in different types of cancer...
2018: American Journal of Cancer Research
Tobias Brandmann, Hana Fakim, Zoya Padamsi, Ji-Young Youn, Anne-Claude Gingras, Marc R Fabian, Martin Jinek
The LSM domain-containing protein LSM14/Rap55 plays a role in mRNA decapping, translational repression, and RNA granule (P-body) assembly. How LSM14 interacts with the mRNA silencing machinery, including the eIF4E-binding protein 4E-T and the DEAD-box helicase DDX6, is poorly understood. Here we report the crystal structure of the LSM domain of LSM14 bound to a highly conserved C-terminal fragment of 4E-T. The 4E-T C-terminus forms a bi-partite motif that wraps around the N-terminal LSM domain of LSM14. We also determined the crystal structure of LSM14 bound to the C-terminal RecA-like domain of DDX6...
March 6, 2018: EMBO Journal
Enzo Z Poirier, Bertsy Goic, Lorena Tomé-Poderti, Lionel Frangeul, Jérémy Boussier, Valérie Gausson, Hervé Blanc, Thomas Vallet, Hyelee Loyd, Laura I Levi, Sophie Lanciano, Chloé Baron, Sarah H Merkling, Louis Lambrechts, Marie Mirouze, Susan Carpenter, Marco Vignuzzi, Maria-Carla Saleh
The RNAi pathway confers antiviral immunity in insects. Virus-specific siRNA responses are amplified via the reverse transcription of viral RNA to viral DNA (vDNA). The nature, biogenesis, and regulation of vDNA are unclear. We find that vDNA produced during RNA virus infection of Drosophila and mosquitoes is present in both linear and circular forms. Circular vDNA (cvDNA) is sufficient to produce siRNAs that confer partially protective immunity when challenged with a cognate virus. cvDNAs bear homology to defective viral genomes (DVGs), and DVGs serve as templates for vDNA and cvDNA synthesis...
February 27, 2018: Cell Host & Microbe
Julien Brustel, Zuzanna Kozik, Natalia Gromak, Velibor Savic, Steve M M Sweet
Deletions and chromosome re-arrangements are common features of cancer cells. We have established a new two-component system reporting on epigenetic silencing or deletion of an actively transcribed gene adjacent to a double-strand break (DSB). Unexpectedly, we find that a targeted DSB results in a minority (<10%) misrepair event of kilobase deletions encompassing the DSB site and transcribed gene. Deletions are reduced upon RNaseH1 over-expression and increased after knockdown of the DNA:RNA helicase Senataxin, implicating a role for DNA:RNA hybrids...
March 1, 2018: Scientific Reports
Benjamin Götte, Lifeng Liu, Gerald M McInerney
Alphaviruses encode 4 non-structural proteins (nsPs), most of which have well-understood functions in capping and membrane association (nsP1), polyprotein processing and RNA helicase activity (nsP2) and as RNA-dependent RNA polymerase (nsP4). The function of nsP3 has been more difficult to pin down and it has long been referred to as the more enigmatic of the nsPs. The protein comprises three domains, an N-terminal macro domain, a central zinc-binding domain and a C-terminal hypervariable domain (HVD). In this article, we review old and new literature about the functions of the three domains...
February 28, 2018: Viruses
Georgios Kellaris, Kamal Khan, Shahid M Baig, I-Chun Tsai, Francisca Millan Zamora, Paul Ruggieri, Marvin R Natowicz, Nicholas Katsanis
BACKGROUND: Intellectual disability (ID) is a common condition with a population prevalence frequency of 1-3% and an enrichment for males, driven in part by the contribution of mutant alleles on the X-chromosome. Among the more than 500 genes associated with ID, DDX3X represents an outlier in sex specificity. Nearly all reported pathogenic variants of DDX3X are de novo, affect mostly females, and appear to be loss of function variants, consistent with the hypothesis that haploinsufficiency at this locus on the X-chromosome is likely to be lethal in males...
March 1, 2018: Human Genomics
Jan Wollenhaupt, Lisa M Henning, Jana Sticht, Christian Becke, Christian Freund, Karine F Santos, Markus C Wahl
Precursor messenger RNA splicing is mediated by the spliceosome, a large and dynamic molecular machine composed of five small nuclear RNAs and numerous proteins. Many spliceosomal proteins are predicted to be intrinsically disordered or contain large disordered regions, but experimental validation of these predictions is scarce, and the precise functions of these proteins are often unclear. Here, we show via circular dichroism spectroscopy, dynamic light scattering, and NMR spectroscopy that the yeast spliceosomal disassembly factor Ntr2 is largely intrinsically disordered...
February 27, 2018: Biophysical Journal
Katherine E Sloan, Markus T Bohnsack
RNA helicases are critical regulators at the nexus of multiple pathways of RNA metabolism, and in the complex cellular environment, tight spatial and temporal regulation of their activity is essential. Dedicated protein cofactors play key roles in recruiting helicases to specific substrates and modulating their catalytic activity. Alongside individual RNA helicase cofactors, networks of cofactors containing evolutionarily conserved domains such as the G-patch and MIF4G domains highlight the potential for cross-regulation of different aspects of gene expression...
February 24, 2018: Trends in Biochemical Sciences
Cédric Nadiras, Annie Schwartz, Mildred Delaleau, Marc Boudvillain
Besides their well-known posttranscriptional effects on mRNA translation and decay, sRNAs and associated RNA chaperones (e.g., Hfq, CsrA) sometimes regulate gene expression at the transcriptional level. In this case, the sRNA-dependent machinery modulates the activity of the transcription termination factor Rho, a ring-shaped RNA translocase/helicase that dissociates transcription elongation complexes at specific loci of the bacterial genome. Here, we describe biochemical assays to detect Rho-dependent termination signals in genomic regions of interest and to assess the effects of sRNAs and/or associated RNA chaperones on such signals...
2018: Methods in Molecular Biology
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