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https://www.readbyqxmd.com/read/28224203/nucleic-acid-sensing-pattern-recognition-receptors-in-the-development-of-colorectal-cancer-and-colitis
#1
REVIEW
Liangmei He, Yayun Chen, Yuanbing Wu, Ying Xu, Zixiang Zhang, Zhiping Liu
Colorectal cancer (CRC) is a leading cause of cancer-related deaths that is often associated with inflammation initiated by activation of pattern recognition receptors (PRRs). Nucleic acid sensing PRRs are one of the major subsets of PRRs that sense nucleic acid (DNA and RNA), mainly including some members of Toll-like receptors (TLR3, 7, 8, 9), AIM2-like receptors (AIM2, IFI16), STING, cGAS, RNA polymerase III, and DExD/H box nucleic acid helicases (such as RIG-I like receptors (RIG-I, MDA5, LPG2), DDX1, 3, 5, 7, 17, 21, 41, 60, and DHX9, 36)...
February 21, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28223711/identification-of-novel-cancer-therapeutic-targets-using-a-designed-and-pooled-shrna-library-screen
#2
David Oliver, Hao Ji, Piaomu Liu, Alexander Gasparian, Ellen Gardiner, Samuel Lee, Adrian Zenteno, Lillian O Perinskaya, Mengqian Chen, Phillip Buckhaults, Eugenia Broude, Michael D Wyatt, Homayoun Valafar, Edsel Peña, Michael Shtutman
Targeted cancer therapeutics aim to exploit tumor-specific, genetic vulnerabilities specifically affecting neoplastic cells without similarly affecting normal cells. Here we performed sequencing-based screening of an shRNA library on a panel of cancer cells of different origins as well as normal cells. The shRNA library was designed to target a subset of genes previously identified using a whole genome screening approach. This focused shRNA library was infected into cells followed by analysis of enrichment and depletion of the shRNAs over the course of cell proliferation...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28223502/cryo-em-structure-of-the-replisome-reveals-multiple-interactions-coordinating-dna-synthesis
#3
Arkadiusz W Kulczyk, Arne Moeller, Peter Meyer, Piotr Sliz, Charles C Richardson
We present a structure of the ∼650-kDa functional replisome of bacteriophage T7 assembled on DNA resembling a replication fork. A structure of the complex consisting of six domains of DNA helicase, five domains of RNA primase, two DNA polymerases, and two thioredoxin (processivity factor) molecules was determined by single-particle cryo-electron microscopy. The two molecules of DNA polymerase adopt a different spatial arrangement at the replication fork, reflecting their roles in leading- and lagging-strand synthesis...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28221134/human-nup98-regulates-the-localization-and-activity-of-dexh-d-box-helicase-dhx9
#4
Juliana S Capitanio, Ben Montpetit, Richard W Wozniak
Beyond their role at nuclear pore complexes, some nucleoporins function in the nucleoplasm. One such nucleoporin, Nup98, binds chromatin and regulates gene expression. To gain insight into how Nup98 contributes to this process, we focused on identifying novel binding partners and understanding the significance of these interactions. Here we report on the identification of the DExH/D-box helicase DHX9 as an intranuclear Nup98 binding partner. Various results, including in vitro assays, show that the FG/GLFG region of Nup98 binds to N- and C-terminal regions of DHX9 in an RNA facilitated manner...
February 21, 2017: ELife
https://www.readbyqxmd.com/read/28217257/regulation-of-hepatic-microrna-expression-by-hepatocyte-nuclear-factor-4-alpha
#5
Hong Lu, Xiaohong Lei, Jerry Liu, Curtis Klaassen
AIM: To uncover the role of hepatocyte nuclear factor 4 alpha (HNF4α) in regulating hepatic expression of microRNAs. METHODS: Microarray and real-time PCR were used to determine hepatic expression of microRNAs in young-adult mice lacking Hnf4α expression in liver (Hnf4α-LivKO). Integrative genomics viewer software was used to analyze the public chromatin immunoprecipitation-sequencing datasets for DNA-binding of HNF4α, RNA polymerase-II, and histone modifications to loci of microRNAs in mouse liver and human hepatoma cells...
February 8, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28217125/the-structure-and-function-of-the-gram-positive-bacterial-rna-degradosome
#6
REVIEW
Kyu Hong Cho
The RNA degradosome is a highly structured protein complex responsible for bulk RNA decay in bacteria. The main components of the complex, ribonucleases, an RNA helicase, and glycolytic enzymes are well-conserved in bacteria. Some components of the degradosome are essential for growth and the disruption of degradosome formation causes slower growth, indicating that this complex is required for proper cellular function. The study of the Escherichia coli degradosome has been performed extensively for the last several decades and has revealed detailed information on its structure and function...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28216662/ddx5-promotes-gastric-cancer-cell-proliferation-in-vitro-and-in-vivo-through-mtor-signaling-pathway
#7
Cheng Du, Dan-Qi Li, Na Li, Li Chen, Shi-Sen Li, Yang Yang, Ming-Xiao Hou, Man-Jiang Xie, Zhen-Dong Zheng
DEAD (Asp-Glu-Ala-Asp) box helicase 5 (DDX5) is an ATP-dependent RNA helicase that is overexpressed in various malignancies. Increasing evidence suggests that DDX5 participates in carcinogenesis and cancer progression via promoting cell proliferation and metastasis. However, the functional role of DDX5 in gastric cancer is largely unknown. In this study, we observed that DDX5 was significantly up-regulated in gastric cancer tissues compared with the paired adjacent normal tissues. The expression of DDX5 correlated strongly with Ki67 index and pathological stage of gastric cancer...
February 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28212935/dissecting-biochemical-peculiarities-of-the-atpase-activity-of-tcsub2-a-component-of-the-mrna-export-pathway-in-trypanosoma-cruzi
#8
Ize de Aguiar Bittencourt, Mariana Serpeloni, Priscila Mazzochi Hiraiwa, Tatiana de Arruda Campos Brasil de Souza, Andréa Rodrigues Ávila
The RNA helicase DEAD-box protein Sub2 (yeast)/UAP56 (mammals) is conserved across eukaryotes and is essential for mRNA export in trypanosomes. Despite the high conservation of Sub2 in lower eukaryotes such as Trypanosoma cruzi, the low conservation of other mRNA export factors raises questions regarding whether the mode of action of TcSub2 is similar to that of orthologs from other eukaryotes. Mutation of the conserved K87 residue of TcSub2 abolishes ATPase activity, showing that its ATPase domain is functional...
February 14, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28203524/in-vivo-mapping-of-a-dynamic-ribonucleoprotein-granule-interactome-in-early-drosophila-embryos
#9
Jimiao Zheng, Ming Gao, Nhan Huynh, Samuel J Tindell, Hieu D L Vo, W Hayes McDonald, Alexey L Arkov
Macromolecular complexes and organelles play crucial roles within cells, but their native architectures are often unknown. Here, we use an evolutionarily conserved germline organelle, the germ granule, as a paradigm. In Drosophila embryos, we map one of its interactomes using a novel in vivo crosslinking approach that employs two interacting granule proteins and determines their common neighbor molecules. We identified an in vivo granule assembly of Tudor, Aubergine, motor and metabolic proteins, and RNA helicases, and provide evidence for direct interactions within this assembly using purified components...
December 2016: FEBS Open Bio
https://www.readbyqxmd.com/read/28202376/structural-features-of-zika-virus-non-structural-proteins-3-and-5-and-its-individual-domains-in-solution-as-well-as-insights-into-ns3-inhibition
#10
Wuan Geok Saw, Ankita Pan, Malathy Sony Subramanian Manimekalai, Gerhard Grüber
Zika virus (ZIKV) has emerged as a pathogen of major health concern. The virus relies on its non-structural protein 5 (NS5) including a methyl-transferase (MTase) and a RNA-dependent RNA polymerase (RdRp) for capping and synthesis of the viral RNA and the nonstructural protein 3 (NS3) with its protease and helicase domain for polyprotein possessing, unwinding dsRNA proceeding replication, and NTPase/RTPase activities. In this study we present for the first time insights into the overall structure of the entire French Polynesia ZIKV NS3 in solution...
February 12, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28191733/a-novel-dynamic-expression-of-vasa-in-male-germ-cells-during-spermatogenesis-in-the-chinese-soft-shell-turtle-pelidiscus-sinensis
#11
Wei Li, Piaoyi Zhang, Xuling Wu, Xinping Zhu, Hongyan Xu
vasa gene encodes a highly conserved DEAD-box RNA helicase, required for germ cell development across animal kingdom. Vasa mutations cause male infertility in mammals. It has been widely used as a biomarker for studying animal fertility or manipulating germ cells in organisms. However, in reptilians, the functions of vasa gene involved in germ cell differentiation are largely unclear; this hampers the development of biological techniques and the improvement of the productivity in these species. Here a vasa cDNA was isolated in Chinese soft-shell turtle and it predicts a protein of 691 amino acid residues, which is 72%, 69%, 58%, 59%, and 54-56% identical to its homolog from mouse, platypus, frog, chicken, and fish, respectively, and named as PsVasa...
February 13, 2017: Journal of Experimental Zoology. Part B, Molecular and Developmental Evolution
https://www.readbyqxmd.com/read/28190795/progress-in-understanding-the-molecular-functions-of-ddx3y-dby-in-male-germ-cell-development-and-maintenance
#12
Alexei A Kotov, Oxana M Olenkina, Baira K Godneeva, Vladimir E Adashev, Ludmila V Olenina
Human DDX3 paralogs are housed on the X chromosome (DDX3X) as well as in the non- recombining region Yq11 of the Y-chromosome (DDX3Y or DBY). A gene encoding RNA helicase DDX3Y is located in the AZoospermia Factor a (AZFa) region of the Y-chromosome and expressed only in male germ cells. Deletions encompassing the DDX3Y gene lead to azoospermia and cause Sertoli Cell-Only Syndrome (SCOS) in humans. SCOS is characterized by a complete germ cell lack with preservation of somatic Sertoli cells. This review summarizes current advances in the study of DDX3Y functions in maintenance and development of early male germ cells...
February 12, 2017: Bioscience Trends
https://www.readbyqxmd.com/read/28181036/ddx50-inhibits-the-replication-of-dengue-virus-2-by-upregulating-ifn-%C3%AE-production
#13
Peijun Han, Wei Ye, Xin Lv, Hongwei Ma, Daihui Weng, Yangchao Dong, Linfeng Cheng, Hesong Chen, Liang Zhang, Zhikai Xu, Yingfeng Lei, Fanglin Zhang
Dengue virus (DENV) infects approximately 390 million people per year, and each of the four DENV serotypes (DENV-1, DENV-2, DENV-3, and DENV-4) is capable of causing infection. At present, there is no antiviral drug available for the treatment of DENV. Several DExD/H-box helicases have been shown to be involved in the antiviral immune response or viral replication. In the present study, we investigated the role of DDX50 in DENV-2 RNA replication. Our data showed that the level of DENV-2 RNA increased in DDX50 knockdown cells during an early stage of viral infection and decreased in DDX50-overexpressing cells...
February 8, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28180304/rna-helicase-ddx19-stabilizes-ribosomal-elongation-and-termination-complexes
#14
Tatiana Mikhailova, Ekaterina Shuvalova, Alexander Ivanov, Denis Susorov, Alexey Shuvalov, Peter M Kolosov, Elena Alkalaeva
No abstract text is available yet for this article.
February 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28178669/ercc6l-a-dna-helicase-is-involved-in-cell-proliferation-and-associated-with-survival-and-progress-in-breast-and-kidney-cancers
#15
Shao-Yan Pu, Qin Yu, Huan Wu, Jian-Jun Jiang, Xiao-Qiong Chen, Yong-Han He, Qing-Peng Kong
By analyzing 4987 cancer transcriptomes from The Cancer Genome Atlas (TCGA), we identified that excision repair cross-complementation group 6 like (ERCC6L), a newly discovered DNA helicase, is highly expressed in 12 solid cancers. However, its role and mechanism in tumorigenesis are largely unknown. In this study, we found that ERCC6L silencing by small interring RNA (siRNA) or short hairpin RNA (shRNA) significantly inhibited the proliferation of breast (MCF-7, MDA-MB-231) and kidney cancer cells (786-0). Furthermore, ERCC6L silencing induced cell cycle arrest at G0/G1 phase without affecting apoptosis...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28160601/the-structure-and-function-of-an-rna-polymerase-interaction-domain-in-the-pcra-uvrd-helicase
#16
Kelly Sanders, Chia-Liang Lin, Abigail J Smith, Nora Cronin, Gemma Fisher, Vasileios Eftychidis, Peter McGlynn, Nigel J Savery, Dale B Wigley, Mark S Dillingham
No abstract text is available yet for this article.
February 4, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28157507/transcription-without-xpb-establishes-a-unified-helicase-independent-mechanism-of-promoter-opening-in-eukaryotic-gene-expression
#17
Sergey Alekseev, Zita Nagy, Jérémy Sandoz, Amélie Weiss, Jean-Marc Egly, Nicolas Le May, Frederic Coin
Transcription starts with the assembly of pre-initiation complexes on promoters followed by their opening. Current models suggest that class II gene transcription requires ATP and the TFIIH XPB subunit to open a promoter. Here, we observe that XPB depletion surprisingly leaves transcription virtually intact. In contrast, inhibition of XPB ATPase activity affects transcription, revealing that mRNA expression paradoxically accommodates the absence of XPB while being sensitive to the inhibition of its ATPase activity...
February 2, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28153748/a-dead-box-helicase-mediates-an-rna-structural-transition-in-the-hiv-1-rev-response-element
#18
John A Hammond, Rajan Lamichhane, David P Millar, James R Williamson
Nuclear export of partially spliced or unspliced HIV-1 RNA transcripts requires binding of the viral protein regulator of expression of virion (Rev) to the Rev response element (RRE) and subsequent oligomerization in a cooperative manner. Cellular DEAD-box helicase DEAD-box protein 1 (DDX1) plays a role in HIV replication, interacting with and affecting Rev-containing HIV transcripts in vivo, interacting directly with the RRE and Rev in vitro, and promoting Rev oligomerization in vitro. Binding of DDX1 results in enhancement of Rev oligomerization on the RRE that is correlated with an RNA structural change within the RRE that persists even after dissociation of DDX1...
January 31, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28148788/the-atp-dependent-rna-helicase-ddx3x-modulates-herpes-simplex-virus-type-1-gene-expression
#19
Bita Khadivjam, Camille Stegen, Marc-Aurèle Hogue-Racine, Nabil El Bilali, Katinka Döhner, Beate Sodeik, Roger Lippé
: The human protein DDX3X is a DEAD-box ATP-dependent RNA helicase that regulates transcription, mRNA maturation, mRNA export and translation. DDX3X concomitantly modulates the replication of several RNA viruses and promotes innate immunity. We previously showed that herpes simplex virus type 1 (HSV-1), a human DNA virus, incorporates DDX3X into its mature particles and that DDX3X is required for optimal HSV-1 infectivity. Here, we show that viral gene expression, replication and propagation depend on optimal DDX3X protein levels...
February 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28138868/combination-treatment-using-ddx3-and-parp-inhibitors-induces-synthetic-lethality-in-brca1-proficient-breast-cancer
#20
Marise R Heerma van Voss, Justin D Brilliant, Farhad Vesuna, Guus M Bol, Elsken van der Wall, Paul J van Diest, Venu Raman
Triple-negative breast cancers have unfavorable outcomes due to their inherent aggressive behavior and lack of targeted therapies. Breast cancers occurring in BRCA1 mutation carriers are mostly triple-negative and harbor homologous recombination deficiency, sensitizing them to inhibition of a second DNA damage repair pathway by, e.g., PARP inhibitors. Unfortunately, resistance against PARP inhibitors in BRCA1-deficient cancers is common and sensitivity is limited in BRCA1-proficient breast cancers. RK-33, an inhibitor of the RNA helicase DDX3, was previously demonstrated to impede non-homologous end-joining repair of DNA breaks...
March 2017: Medical Oncology
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