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https://www.readbyqxmd.com/read/28087495/comparative-analysis-of-variation-and-selection-in-the-hcv-genome
#1
Juan Ángel Patiño-Galindo, Fernando González-Candelas
Genotype 1 of the hepatitis C virus (HCV) is the most prevalent of the variants of this virus. Its two main subtypes, HCV-1a and HCV-1b, are associated to differences in epidemic features and risk groups, despite sharing similar features in most biological properties. We have analyzed the impact of positive selection on the evolution of these variants using complete genome coding regions, and compared the levels of genetic variability and the distribution of positively selected sites. We have also compared the distributions of positively selected and conserved sites considering different factors such as RNA secondary structure, the presence of different epitopes (antibody, CD4 and CD8), and secondary protein structure...
January 10, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28077601/a-new-rna-based-adjuvant-enhances-virus-specific-vaccine-responses-by-locally-triggering-tlr-and-rlh-dependent-effects
#2
Annett Ziegler, Claudia Soldner, Stefan Lienenklaus, Julia Spanier, Stephanie Trittel, Peggy Riese, Thomas Kramps, Siegfried Weiss, Regina Heidenreich, Edith Jasny, Carlos A Guzmán, Karl-Josef Kallen, Mariola Fotin-Mleczek, Ulrich Kalinke
Among innovative adjuvants conferring a Th1-shift, RNAdjuvant is a promising candidate. This adjuvant consists of a 547-nt uncapped noncoding ssRNA containing polyU repeats that is stabilized by a cationic carrier peptide. Whereas vaccination of mice with an influenza subunit vaccine induced moderate virus-specific IgG1, vaccination together with RNAdjuvant significantly enhanced this IgG1 and additionally promoted the formation of IgG2b/c, which is indicative of Th1 responses. Furthermore, such sera neutralized influenza virus, whereas this effect was not detected upon vaccination with the subunit vaccine alone...
January 11, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28076779/transcription-dynamics-prevent-rna-mediated-genomic-instability-through-srpk2-dependent-ddx23-phosphorylation
#3
Sreerama Chaitanya Sridhara, Sílvia Carvalho, Ana Rita Grosso, Lina Marcela Gallego-Paez, Maria Carmo-Fonseca, Sérgio Fernandes de Almeida
Genomic instability is frequently caused by nucleic acid structures termed R-loops that are formed during transcription. Despite their harmful potential, mechanisms that sense, signal, and suppress these structures remain elusive. Here, we report that oscillations in transcription dynamics are a major sensor of R-loops. We show that pausing of RNA polymerase II (RNA Pol II) initiates a signaling cascade whereby the serine/arginine protein kinase 2 (SRPK2) phosphorylates the DDX23 helicase, culminating in the suppression of R-loops...
January 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28076346/cryo-em-structure-of-a-human-spliceosome-activated-for-step-2-of-splicing
#4
Karl Bertram, Dmitry E Agafonov, Wen-Ti Liu, Olexandr Dybkov, Cindy L Will, Klaus Hartmuth, Henning Urlaub, Berthold Kastner, Holger Stark, Reinhard Lu Hrmann
Spliceosome rearrangements facilitated by RNA helicase Prp16 before catalytic step 2 of splicing are poorly understood. Here we report a 3D cryo-electron microscopy structure of the human spliceosomal C complex stalled directly after Prp16 action (C*). The architecture of the catalytic U2-U6 RNP core of the human C* spliceosome is highly similar to that of the yeast pre-Prp16 C complex. However, in C* the branched intron region is separated (by ~20 Å) from the catalytic centre, and its position close to the U6 snRNA ACAGA box is stabilised by interactions with the Prp8 RNase H-like and Prp17 WD40 domains...
January 11, 2017: Nature
https://www.readbyqxmd.com/read/28069994/rhau-helicase-stabilizes-g4-in-its-nucleotide-free-state-and-destabilizes-g4-upon-atp-hydrolysis
#5
Huijuan You, Simon Lattmann, Daniela Rhodes, Jie Yan
The DEAH-box ATP-dependent RHAU helicases specifically unfold RNA and DNA G-quadruplexes (G4s). However, it remains unclear how the RHAU's G4 unfolding activity is coupled to different stages of the ATPase cycle. Here, using a single-molecule manipulation approach, we show that binding of Drosophila RHAU stabilizes an intramolecularly folded parallel DNA G4 against mechanical unfolding in its nucleotide-free and in its AMP-PNP or ADP bound states, while it destabilizes the G4 when coupled to ATP hydrolysis...
January 9, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28069330/top2a-hells-atad2-and-tet3-are-novel-prognostic-markers-in-renal-cell-carcinoma
#6
Dong Chen, Matthias Maruschke, Oliver Hakenberg, Wolfgang Zimmermann, Christian G Stief, Alexander Buchner
OBJECTIVE: To identify and validate novel prognostic marker genes in clear cell renal cell carcinoma (RCC) that are increasingly expressed during tumor progression. METHODS: Total RNA was isolated from normal renal tissue, primary G1 and G3 tumors, 14 samples each, and 32 metastases from RCC patients. Expression profiles were created using oligonucleotide microarrays. Significant gene expression differences (p<0.05) were identified between normal kidney, primary tumor and metastases...
January 6, 2017: Urology
https://www.readbyqxmd.com/read/28065761/g-quadruplexes-unfolding-by-rhau-helicase
#7
Nassima Meriem Gueddouda, Oscar Mendoza, Dennis Gomez, Anne Bourdoncle, Jean-Louis Mergny
G-quadruplexes (G4) are RNA and DNA secondary structures formed by the stacking of guanine quartets in guanine rich sequences. Quadruplex-prone motifs may be found in key genomic regions such as telomeres, ribosomal DNA, transcriptional activators and regulators or oncogene promoters. A number of proteins involved in various biological processes are able to interact with G4s. Among them, proteins dedicated to nucleic acids unwinding such as WRN, BLM, FANCJ or PIF1, can unfold G4 structures. Mutations of these helicases are linked to genome instability and to increases in cancer risks...
January 5, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28062043/subangstrom-measurements-of-enzyme-function-using-a-biological-nanopore-sprnt
#8
A H Laszlo, I M Derrrington, J H Gundlach
Nanopores are emerging as new single-molecule tools in the study of enzymes. Based on the progress in nanopore sequencing of DNA, a tool called Single-molecule Picometer Resolution Nanopore Tweezers (SPRNT) was developed to measure the movement of enzymes along DNA in real time. In this new method, an enzyme is loaded onto a DNA (or RNA) molecule. A single-stranded DNA end of this complex is drawn into a nanopore by an electrostatic potential that is applied across the pore. The single-stranded DNA passes through the pore's constriction until the enzyme comes into contact with the pore...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28057895/gibberellin-signaling-requires-chromatin-remodeler-pickle-to-promote-vegetative-growth-and-phase-transitions
#9
Jeongmoo Park, Dong-Ha Oh, Maheshi Dassanayake, Khoa Thi Nguyen, Joe Ogas, Giltsu Choi, Tai-Ping Sun
PICKLE (PKL) is an ATP-dependent Chromodomain-Helicase-DNA-binding domain (CHD3) chromatin remodeling enzyme in Arabidopsis thaliana. Previous studies showed that PKL promotes embryonic-to-vegetative transition by inhibiting expression of seed-specific genes during seed germination. The pkl mutants display a low penetrance of the 'pickle root' phenotype with a thick and green primary root that retains embryonic characteristics. The penetrance of this pickle root phenotype in pkl is dramatically increased in GA-deficient conditions...
January 5, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28056029/hcv-induces-telomerase-reverse-transcriptase-increases-its-catalytic-activity-and-promotes-caspase-degradation-in-infected-human-hepatocytes
#10
Zhaowen Zhu, Huy Tran, M Meleah Mathahs, Thomas O Moninger, Warren N Schmidt
INTRODUCTION: Telomerase repairs the telomeric ends of chromosomes and is active in nearly all malignant cells. Hepatitis C virus (HCV) is known to be oncogenic and potential interactions with the telomerase system require further study. We determined the effects of HCV infection on human telomerase reverse transcriptase (TERT) expression and enzyme activity in primary human hepatocytes and continuous cell lines. RESULTS: Primary human hepatocytes and Huh-7.5 hepatoma cells showed early de novo TERT protein expression 2-4 days after infection and these events coincided with increased TERT promoter activation, TERT mRNA, and telomerase activity...
2017: PloS One
https://www.readbyqxmd.com/read/28035044/a-role-for-gle1-a-regulator-of-dead-box-rna-helicases-at-centrosomes-and-basal-bodies
#11
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
#12
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/28025139/the-rna-helicase-ddx39b-and-its-paralog-ddx39a-regulate-androgen-receptor-splice-variant-ar-v7-generation
#13
Daisuke Nakata, Shoichi Nakao, Kazuhide Nakayama, Shinsuke Araki, Yusuke Nakayama, Samuel Aparicio, Takahito Hara, Atsushi Nakanishi
Mounting evidence suggests that constitutively active androgen receptor (AR) splice variants, typified by AR-V7, are associated with poor prognosis and resistance to androgen deprivation therapy in prostate cancer patients. However, mechanisms governing the generation of AR splice variants are not fully understood. In this study, we aimed to investigate the dynamics of AR splice variant generation using the JDCaP prostate cancer model that expresses AR splice variants under androgen depletion. Microarray analysis of JDCaP xenografts before and after expression of AR splice variants suggested that dysregulation of RNA processing pathways is likely involved in AR splice variant generation...
December 23, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28024153/hiv-1-blocks-the-signaling-adaptor-mavs-to-evade-antiviral-host-defense-after-sensing-of-abortive-hiv-1-rna-by-the-host-helicase-ddx3
#14
Sonja I Gringhuis, Nina Hertoghs, Tanja M Kaptein, Esther M Zijlstra-Willems, Ramin Sarrami-Fooroshani, Joris K Sprokholt, Nienke H van Teijlingen, Neeltje A Kootstra, Thijs Booiman, Karel A van Dort, Carla M S Ribeiro, Agata Drewniak, Teunis B H Geijtenbeek
The mechanisms by which human immunodeficiency virus 1 (HIV-1) avoids immune surveillance by dendritic cells (DCs), and thereby prevents protective adaptive immune responses, remain poorly understood. Here we showed that HIV-1 actively arrested antiviral immune responses by DCs, which contributed to efficient HIV-1 replication in infected individuals. We identified the RNA helicase DDX3 as an HIV-1 sensor that bound abortive HIV-1 RNA after HIV-1 infection and induced DC maturation and type I interferon responses via the signaling adaptor MAVS...
December 26, 2016: Nature Immunology
https://www.readbyqxmd.com/read/28008922/atp-hydrolysis-by-upf1-is-required-for-efficient-translation-termination-at-premature-stop-codons
#15
Lucas D Serdar, DaJuan L Whiteside, Kristian E Baker
Nonsense-mediated mRNA decay (NMD) represents a eukaryotic quality control pathway that recognizes and rapidly degrades transcripts harbouring nonsense mutations to limit accumulation of non-functional and potentially toxic truncated polypeptides. A critical component of the NMD machinery is UPF1, an RNA helicase whose ATPase activity is essential for NMD, but for which the precise function and site of action remain unclear. We provide evidence that ATP hydrolysis by UPF1 is required for efficient translation termination and ribosome release at a premature termination codon...
December 23, 2016: Nature Communications
https://www.readbyqxmd.com/read/28004253/a-novel-single-stranded-rna-virus-in-nesidiocoris-tenuis
#16
Pengjun Xu, Xueru Song, Xianming Yang, Zhaoqi Tang, Guangwei Ren, Yanhui Lu
The complete genome sequence of a novel single-stranded RNA virus in Nesidiocoris tenuis was determined by RNA-seq and rapid amplification of cDNA ends (RACE) methodologies and was named N. tenuis virus 1. The genomic RNA was 3970 nucleotides (nt) in length and contained two putative open reading frames (ORFs). ORF1 encoded a polypeptide with 283 amino acids containing a viral (superfamily 1) RNA helicase (Hel) domain, and ORF2 encoded a polypeptide with 294 amino acids containing an RNA-dependent RNA polymerase (RdRP) domain...
December 21, 2016: Archives of Virology
https://www.readbyqxmd.com/read/28004241/the-arabidopsis-tho-trex-component-tex1-functionally-interacts-with-mos11-and-modulates-mrna-export-and-alternative-splicing-events
#17
Brian B Sørensen, Hans F Ehrnsberger, Silvia Esposito, Alexander Pfab, Astrid Bruckmann, Judith Hauptmann, Gunter Meister, Rainer Merkl, Thomas Schubert, Gernot Längst, Michael Melzer, Marion Grasser, Klaus D Grasser
We identify proteins that associate with the THO core complex, and show that the TEX1 and MOS11 components functionally interact, affecting mRNA export and splicing as well as plant development. TREX (TRanscription-EXport) is a multiprotein complex that plays a central role in the coordination of synthesis, processing and nuclear export of mRNAs. Using targeted proteomics, we identified proteins that associate with the THO core complex of Arabidopsis TREX. In addition to the RNA helicase UAP56 and the mRNA export factors ALY2-4 and MOS11 we detected interactions with the mRNA export complex TREX-2 and multiple spliceosomal components...
December 21, 2016: Plant Molecular Biology
https://www.readbyqxmd.com/read/28003473/primase-is-required-for-helicase-activity-and-helicase-alters-the-specificity-of-primase-in-the-enteropathogen-clostridium-difficile
#18
Erika van Eijk, Vasileios Paschalis, Matthew Green, Annemieke H Friggen, Marilynn A Larson, Keith Spriggs, Geoffrey S Briggs, Panos Soultanas, Wiep Klaas Smits
DNA replication is an essential and conserved process in all domains of life and may serve as a target for the development of new antimicrobials. However, such developments are hindered by subtle mechanistic differences and limited understanding of DNA replication in pathogenic microorganisms. Clostridium difficile is the main cause of healthcare-associated diarrhoea and its DNA replication machinery is virtually uncharacterized. We identify and characterize the mechanistic details of the putative replicative helicase (CD3657), helicase-loader ATPase (CD3654) and primase (CD1454) of C...
December 2016: Open Biology
https://www.readbyqxmd.com/read/28000744/mechanical-unfolding-kinetics-of-the-srv-1-gag-pro-mrna-pseudoknot-possible-implications-for-1-ribosomal-frameshifting-stimulation
#19
Zhensheng Zhong, Lixia Yang, Haiping Zhang, Jiahao Shi, J Jeya Vandana, Do Thuy Uyen Ha Lam, René C L Olsthoorn, Lanyuan Lu, Gang Chen
Minus-one ribosomal frameshifting is a translational recoding mechanism widely utilized by many RNA viruses to generate accurate ratios of structural and catalytic proteins. An RNA pseudoknot structure located in the overlapping region of the gag and pro genes of Simian Retrovirus type 1 (SRV-1) stimulates frameshifting. However, the experimental characterization of SRV-1 pseudoknot (un)folding dynamics and the effect of the base triple formation is lacking. Here, we report the results of our single-molecule nanomanipulation using optical tweezers and theoretical simulation by steered molecular dynamics...
December 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27999982/the-prognostic-effect-of-ddx3-upregulation-in-distant-breast-cancer-metastases
#20
Marise R Heerma van Voss, Willemijne A M E Schrijver, Natalie D Ter Hoeve, Laurien D Hoefnagel, Quirine F Manson, Elsken van der Wall, Venu Raman, Paul J van Diest
Metastatic breast cancer remains one of the leading causes of death in women and identification of novel treatment targets is therefore warranted. Functional studies showed that the RNA helicase DDX3 promotes metastasis, but DDX3 expression was never studied in patient samples of metastatic cancer. In order to validate previous functional studies and to evaluate DDX3 as a potential therapeutic target, we investigated DDX3 expression in paired samples of primary and metastatic breast cancer. Samples from 79 breast cancer patients with distant metastases at various anatomical sites were immunohistochemically stained for DDX3...
December 20, 2016: Clinical & Experimental Metastasis
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