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Rna helicase

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https://www.readbyqxmd.com/read/27915293/molecular-mechanism-of-divalent-metal-induced-activation-of-ns3-helicase-and-insights-into-zika-virus-inhibitor-design
#1
Xiaocong Cao, Yajuan Li, Xiangyu Jin, Yuelong Li, Feng Guo, Tengchuan Jin
Zika virus has attracted increasing attention because of its potential for causing human neural disorders, including microcephaly in infants and Guillain-Barré syndrome. Its NS3 helicase domain plays critical roles in NTP-dependent RNA unwinding and translocation during viral replication. Our structural analysis revealed a pre-activation state of NS3 helicase in complex with GTPγS, in which the triphosphate adopts a compact conformation in the absence of any divalent metal ions. In contrast, in the presence of a divalent cation, GTPγS adopts an extended conformation, and the Walker A motif undergoes substantial conformational changes...
December 1, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27902925/targeted-inhibition-of-wrn-helicase-replication-stress-and-cancer
#2
REVIEW
Natalie Orlovetskie, Raphael Serruya, Ghada Abboud-Jarrous, Nayef Jarrous
WRN helicase has several roles in genome maintenance, such as replication, base excision repair, recombination, DNA damage response and transcription. These processes are often found upregulated in human cancers, many of which display increased levels of WRN. Therefore, directed inhibition of this RecQ helicase could be beneficial to selective cancer therapy. Inhibition of WRN is feasible by the use of small-molecule inhibitors or application of RNA interference and EGS/RNase P targeting systems. Remarkably, helicase depletion leads to a severe reduction in cell viability due to mitotic catastrophe, which is triggered by replication stress induced by DNA repair failure and fork progression arrest...
November 27, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27885504/plant-dicer-like-proteins-double-stranded-rna-cleaving-enzymes-for-small-rna-biogenesis
#3
Akihito Fukudome, Toshiyuki Fukuhara
Dicer, a double-stranded RNA (dsRNA)-specific endoribonuclease, plays an essential role in triggering both transcriptional and post-transcriptional gene silencing in eukaryotes by cleaving dsRNAs or single-stranded RNAs bearing stem-loop structures such as microRNA precursor transcripts into 21- to 24-nt small RNAs. Unlike animals, plants have evolved to utilize at least four Dicer-like (DCL) proteins. Extensive genetic studies have revealed that each DCL protein participates in a specific gene silencing pathway, with some redundancy...
November 24, 2016: Journal of Plant Research
https://www.readbyqxmd.com/read/27880071/interplay-of-cis-and-trans-regulatory-mechanisms-in-the-spliceosomal-rna-helicase-brr2
#4
Eva Absmeier, Christian Becke, Jan Wollenhaupt, Karine F Santos, Markus C Wahl
RNA helicase Brr2 is implicated in multiple phases of pre-mRNA splicing and thus requires tight regulation. Brr2 can be auto-inhibited via a large N-terminal region folding back onto its helicase core and auto-activated by a catalytically inactive C-terminal helicase cassette. Furthermore, it can be regulated in trans by the Jab1 domain of the Prp8 protein, which can inhibit Brr2 by intermittently inserting a C-terminal tail in the enzyme's RNA-binding tunnel or activate the helicase after removal of this tail...
November 23, 2016: Cell Cycle
https://www.readbyqxmd.com/read/27871370/enhanced-detection-of-rna-by-mmlv-reverse-transcriptase-coupled-with-thermostable-dna-polymerase-and-dna-rna-helicase
#5
Hiroyuki Okano, Yuta Katano, Misato Baba, Ayako Fujiwara, Ryota Hidese, Shinsuke Fujiwara, Itaru Yanagihara, Tsukasa Hayashi, Kenji Kojima, Teisuke Takita, Kiyoshi Yasukawa
Detection of mRNA is a valuable method for monitoring the specific gene expression. In this study, we devised a novel cDNA synthesis method using three enzymes, the genetically engineered thermostable variant of reverse transcriptase (RT), MM4 (E286R/E302K/L435R/D524A) from Moloney murine leukemia virus (MMLV), the genetically engineered variant of family A DNA polymerase with RT activity, K4polL329A from thermophilic Thermotoga petrophila K4, and the DNA/RNA helicase Tk-EshA from a hyperthermophilic archaeon Thermococcus kodakarensis...
January 2017: Enzyme and Microbial Technology
https://www.readbyqxmd.com/read/27870836/the-rna-helicase-mtr4p-is-a-duplex-sensing-translocase
#6
Eric M Patrick, Sukanya Srinivasan, Eckhard Jankowsky, Matthew J Comstock
The conserved Saccharomyces cerevisiae Ski2-like RNA helicase Mtr4p plays essential roles in eukaryotic nuclear RNA processing. RNA helicase activity of Mtr4p is critical for biological functions of the enzyme, but the molecular basis for RNA unwinding is not understood. Here, single-molecule high-resolution optical trapping measurements reveal that Mtr4p unwinds RNA duplexes by 3'-to-5' translocation on the loading strand, that strand separation occurs in discrete steps of 6 base pairs and that a single Mtr4p molecule performs consecutive unwinding steps...
November 21, 2016: Nature Chemical Biology
https://www.readbyqxmd.com/read/27866900/a-viral-deamidase-targets-the-helicase-domain-of-rig-i-to-block-rna-induced-activation
#7
Jun Zhao, Yi Zeng, Simin Xu, Jie Chen, Guobo Shen, Caiqun Yu, David Knipe, Weiming Yuan, Jian Peng, Wenqing Xu, Chao Zhang, Zanxian Xia, Pinghui Feng
RIG-I detects double-stranded RNA (dsRNA) to trigger antiviral cytokine production. Protein deamidation is emerging as a post-translational modification that chiefly regulates protein function. We report here that UL37 of herpes simplex virus 1 (HSV-1) is a protein deamidase that targets RIG-I to block RNA-induced activation. Mass spectrometry analysis identified two asparagine residues in the helicase 2i domain of RIG-I that were deamidated upon UL37 expression or HSV-1 infection. Deamidation rendered RIG-I unable to sense viral dsRNA, thus blocking its ability to trigger antiviral immune responses and restrict viral replication...
November 16, 2016: Cell Host & Microbe
https://www.readbyqxmd.com/read/27864884/mfd-protein-and-transcription-repair-coupling-in-e-coli
#8
Christopher P Selby
In 1989, transcription-repair coupling (TRC) was first described in Escherichia coli, as the transcription-dependent, preferential nucleotide excision repair (NER) of UV photoproducts located in the template DNA strand. This finding led to pioneering biochemical studies of TRC in the laboratory of Professor Aziz Sancar, where, at the time, major contributions were being made toward understanding the roles of the UvrA, UvrB and UvrC proteins in NER. When the repair studies were extended to TRC, template but not coding strand lesions were found to block RNA polymerase (RNAP) in vitro, and unexpectedly, the blocked RNAP inhibited NER...
November 19, 2016: Photochemistry and Photobiology
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...
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
#10
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/27856760/molecular-mechanisms-of-substrate-controlled-ring-dynamics-and-substepping-in-a-nucleic-acid-dependent-hexameric-motor
#11
Nathan D Thomsen, Michael R Lawson, Lea B Witkowsky, Song Qu, James M Berger
Ring-shaped hexameric helicases and translocases support essential DNA-, RNA-, and protein-dependent transactions in all cells and many viruses. How such systems coordinate ATPase activity between multiple subunits to power conformational changes that drive the engagement and movement of client substrates is a fundamental question. Using the Escherichia coli Rho transcription termination factor as a model system, we have used solution and crystallographic structural methods to delineate the range of conformational changes that accompany distinct substrate and nucleotide cofactor binding events...
November 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27844433/probing-single-helicase-dynamics-on-long-nucleic-acids-through-fluorescence-force-measurement
#12
Chang-Ting Lin, Taekjip Ha
Helicases are nucleic acid-dependent ATPases which can bind and remodel nucleic acids, protein-nucleic acid complexes, or both. They are involved in almost every step in cells related to nucleic acid metabolisms, including DNA replication and repair, transcription, RNA maturation and splicing, and nuclear export processes. Using single-molecule fluorescence-force spectroscopy, we have previously directly observed helicase translocation on long single-stranded DNA and revealed that two monomers of UvrD helicase are required for the initiation of unwinding function...
2017: Methods in Molecular 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
#13
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/27824302/new-insights-into-the-topology-of-the-scanning-ribosome-during-translation-initiation-lessons-from-viruses
#14
René Toribio, Irene Díaz-López, Iván Ventoso
Location of the translation initiation codon generally requires scanning of the 43S ribosomal preinitiation complex (43S PIC) from the 5' of the mRNA. Associated RNA helicases can facilitate movement of the 43S PIC by removing secondary structure present in the 5' UTR of mRNA, which is required for codon inspection. The canonical RNA-dependent helicase eIF4A is directly involved in this process, as part of the eIF4F complex (eIF4G+eIF4A+eIF4E) that associates first with mRNA and then recruits the 43S PIC to initiate scanning...
November 8, 2016: RNA Biology
https://www.readbyqxmd.com/read/27821776/ligand-induced-and-small-molecule-control-of-substrate-loading-in-a-hexameric-helicase
#15
Michael R Lawson, Kevin Dyer, James M Berger
Processive, ring-shaped protein and nucleic acid protein translocases control essential biochemical processes throughout biology and are considered high-prospect therapeutic targets. The Escherichia coli Rho factor is an exemplar hexameric RNA translocase that terminates transcription in bacteria. As with many ring-shaped motor proteins, Rho activity is modulated by a variety of poorly understood mechanisms, including small-molecule therapeutics, protein-protein interactions, and the sequence of its translocation substrate...
November 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27821408/a-novel-translational-control-mechanism-involving-rna-structures-within-coding-sequences
#16
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
#17
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
#18
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/27809838/characterization-of-plasmodium-falciparum-atp-dependent-dna-helicase-ruvb3
#19
Paviga Limudomporn, Saengduen Moonsom, Ubolsree Leartsakulpanich, Pattra Suntornthiticharoen, Songsak Petmitr, Michael Weinfeld, Porntip Chavalitshewinkoon-Petmitr
BACKGROUND: Malaria is one of the most serious and widespread parasitic diseases affecting humans. Because of the spread of resistance in both parasites and the mosquito vectors to anti-malarial drugs and insecticides, controlling the spread of malaria is becoming difficult. Thus, identifying new drug targets is urgently needed. Helicases play key roles in a wide range of cellular activities involving DNA and RNA transactions, making them attractive anti-malarial drug targets. METHODS: ATP-dependent DNA helicase gene (PfRuvB3) of Plasmodium falciparum strain K1, a chloroquine and pyrimethamine-resistant strain, was inserted into pQE-TriSystem His-Strep 2 vector, heterologously expressed and affinity purified...
November 3, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27803702/comparative-profiling-of-mirnas-and-target-gene-identification-in-distant-grafting-between-tomato-and-lycium-goji-berry
#20
A B M Khaldun, Wenjun Huang, Haiyan Lv, Sihong Liao, Shaohua Zeng, Ying Wang
Local translocation of small RNAs between cells is proved. Long distance translocation between rootstock and scion is also well documented in the homo-grafting system, but the process in distant-grafting is widely unexplored where rootstock and scion belonging to different genera. Micro RNAs are a class of small, endogenous, noncoding, gene silencing RNAs that regulate target genes of a wide range of important biological pathways in plants. In this study, tomato was grafted onto goji (Lycium chinense Mill.) to reveal the insight of miRNAs regulation and expression patterns within a distant-grafting system...
2016: Frontiers in Plant Science
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