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transcription Cap binding protein

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https://www.readbyqxmd.com/read/29775646/the-rna-binding-protein-ars2-supports-hematopoiesis-at-multiple-levels
#1
Seerat Elahi, Shawn M Egan, G Aaron Holling, Rachel L Kandefer, Michael J Nemeth, Scott H Olejniczak
Recent biochemical characterization of Arsenic resistance protein 2 (Ars2) has established it as central to determining the fate of nascent RNA polymerase II (RNAPII) transcripts. Through interactions with the nuclear 5'-7-methylguanosine (7mG) cap binding complex (CBC), Ars2 promotes co-transcriptional processing coupled with nuclear export or degradation of several classes of RNAPII transcripts, allowing for gene expression programs that facilitate rapid and sustained proliferation of immortalized cells in culture...
May 15, 2018: Experimental Hematology
https://www.readbyqxmd.com/read/29770522/conclusive-evidence-for-oct4-transcription-in-human-cancer-cell-lines-possible-role-of-a-small-oct4-positive-cancer-cell-population
#2
Tomoyuki Miyamoto, Nobuhiko Mizuno, Mitsuko Kosaka, Yoko Fujitani, Eiji Ohno, Aiji Ohtsuka
The role of octamer-binding transcription factor 4 (OCT4) in human cancer is still debated. Although many studies have been published on human OCT4, determining which of the findings are accurate or which are false-positives is currently challenging. We thus developed the most reliable method to date for highly specific and comprehensive detection of genuine OCT4-transcript variants without false-positive results. Our results provided clear evidence that the transcripts of OCT4A, OCT4B, OCT4B1 and other novel splicing variants are indeed present in many cancer cell lines, but are rarely detected in normal tissue-derived differentiated cells...
May 17, 2018: Stem Cells
https://www.readbyqxmd.com/read/29755485/a-role-of-u12-intron-in-proper-pre-mrna-splicing-of-plant-cap-binding-protein-20-genes
#3
Marcin Pieczynski, Katarzyna Kruszka, Dawid Bielewicz, Jakub Dolata, Michal Szczesniak, Wojciech Karlowski, Artur Jarmolowski, Zofia Szweykowska-Kulinska
The nuclear cap-binding complex (CBC) is composed of two cap-binding proteins: CBP20 and CBP80. The CBP20 gene structure is highly conserved across land plant species. All studied CBP20 genes contain eight exons and seven introns, with the fourth intron belonging to the U12 class. This highly conserved U12 intron always divides the plant CBP20 gene into two parts: one part encodes the core domain containing the RNA binding domain (RBD), and the second part encodes the tail domain with a nuclear localization signal (NLS)...
2018: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29748557/recombinant-amelogenin-regulates-the-bioactivity-of-mouse-cementoblasts-in-vitro
#4
Sema S Hakki, S Buket Bozkurt, Emre Türkay, Michel Dard, Nuhan Purali, Werner Götz
Amelogenin (AMG) is a cell adhesion molecule that has an important role in the mineralization of enamel and regulates events during dental development and root formation. The purpose of the present study was to investigate the effects of recombinant human AMG (rhAMG) on mineralized tissue-associated genes in cementoblasts. Immortalized mouse cementoblasts (OCCM-30) were treated with different concentrations (0.1, 1, 10, 100, 1000, 10,000, 100,000 ng · mL-1 ) of recombinant human AMG (rhAMG) and analyzed for proliferation, mineralization and mRNA expression of bone sialoprotein (BSP), osteocalcin (OCN), collagen type I (COL I), osteopontin (OPN), runt-related transcription factor 2 (Runx2), cementum attachment protein (CAP), and alkaline phosphatase (ALP) genes using quantitative RT-PCR...
May 9, 2018: International Journal of Oral Science
https://www.readbyqxmd.com/read/29721098/capg-enhances-breast-cancer-metastasis-by-competing-with-prmt5-to-modulate-stc-1-transcription
#5
Sheng Huang, Yayun Chi, Yi Qin, Ziliang Wang, Bingqiu Xiu, Yonghui Su, Rong Guo, Liang Guo, Hefen Sun, Chujia Zeng, Shuling Zhou, Xin Hu, Sheng Liu, Zhimin Shao, Zhaohui Wu, Wei Jin, Jiong Wu
Macrophage-capping protein (CAPG) has been shown to promote cancer cell metastasis, although the mechanism remains poorly understood. Methods: Breast cancer (BC) tissue microarray was used to test the role of CAPG in the prognosis of BC patients. Xenograft mice model was used to validate the metastasis promotion role of CAPG in vivo. Gene expression array, chromatin immunoprecipitation and luciferase report assay were performed to search for the target genes of CAPG. Protein immunoprecipitation, MS/MS analysis, tissue microarray and histone methyltransferase assay were used to explore the mechanism of CAPG regulating stanniocalcin 1 (STC-1) transcription...
2018: Theranostics
https://www.readbyqxmd.com/read/29703953/structural-analysis-of-human-ars2-as-a-platform-for-co-transcriptional-rna-sorting
#6
Wiebke Manuela Schulze, Frank Stein, Mandy Rettel, Max Nanao, Stephen Cusack
ARS2 is a highly conserved metazoan protein involved in numerous aspects of nuclear RNA metabolism. As a direct partner of the nuclear cap-binding complex (CBC), it mediates interactions with diverse RNA processing and transport machineries in a transcript-dependent manner. Here, we present the human ARS2 crystal structure, which exhibits similarities and metazoan-specific differences to the plant homologue SERRATE, most notably an additional RRM domain. We present biochemical, biophysical and cellular interactome data comparing wild type and mutant ARS2 that identify regions critical for interactions with FLASH (involved in histone mRNA biogenesis), NCBP3 (a putative cap-binding protein involved in mRNA export) and single-stranded RNA...
April 27, 2018: Nature Communications
https://www.readbyqxmd.com/read/29676910/5-phosphorothiolate-dinucleotide-cap-analogs-reagents-for-mrna-modification-and-potent-small-molecular-inhibitors-of-decapping-enzymes
#7
Blazej Andrzej Wojtczak, Pawel J Sikorski, Kaja Fac-Dabrowska, Anna Nowicka, Marcin Warminski, Dorota Kubacka, Elzbieta Nowak, Marcin Nowotny, Joanna Kowalska, Jacek Jemielity
The 5' cap consists of 7-methylguanosine (m7G) linked by a 5'-5'-triphosphate bridge to mRNA and acts as the master regu-lator of mRNA turnover and translation initiation in eukaryotes. Cap analogs that influence mRNA translation and turnover (either as small molecules or as part of an RNA transcript) are valuable tools for studying gene expression, which is often also of therapeutic relevance. Here, we synthesized a series of 15 dinucleotide cap (m7GpppG) analogs containing a 5'-phosphorothiolate (5'-PSL) moiety (i...
April 20, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29617966/mechrna-prediction-of-lncrna-mechanisms-from-rna-rna-and-rna-protein-interactions
#8
Alexander R Gawronski, Michael Uhl, Yajia Zhang, Yen-Yi Lin, Yashar S Niknafs, Varune R Ramnarine, Rohit Malik, Felix Feng, Arul M Chinnaiyan, Colin C Collins, S Cenk Sahinalp, Rolf Backofen
Motivation: Long non-coding RNAs (lncRNAs) are defined as transcripts longer than 200 nucleotides that do not get translated into proteins. Often these transcripts are processed (spliced, capped, polyadenylated) and some are known to have important biological functions. However, most lncRNAs have unknown or poorly understood functions. Nevertheless, because of their potential role in cancer, lncRNAs are receiving a lot of attention, and the need for computational tools to predict their possible mechanisms of action is more than ever...
April 3, 2018: Bioinformatics
https://www.readbyqxmd.com/read/29601584/2-o-methylation-of-the-mrna-cap-protects-rnas-from-decapping-and-degradation-by-dxo
#9
Frédéric Picard-Jean, Carolin Brand, Maude Tremblay-Létourneau, Andréa Allaire, Maxime C Beaudoin, Simon Boudreault, Cyntia Duval, Julien Rainville-Sirois, Francis Robert, Jerry Pelletier, Brian J Geiss, Martin Bisaillon
The 5' RNA cap structure (m7GpppRNA) is a key feature of eukaryotic mRNAs with important roles in stability, splicing, polyadenylation, mRNA export, and translation. Higher eukaryotes can further modify this minimal cap structure with the addition of a methyl group on the ribose 2'-O position of the first transcribed nucleotide (m7GpppNmpRNA) and sometimes on the adjoining nucleotide (m7GpppNmpNmpRNA). In higher eukaryotes, the DXO protein was previously shown to be responsible for both decapping and degradation of RNA transcripts harboring aberrant 5' ends such as pRNA, pppRNA, GpppRNA, and surprisingly, m7GpppRNA...
2018: PloS One
https://www.readbyqxmd.com/read/29568066/human-transbodies-that-interfere-with-the-functions-of-ebola-virus-vp35-protein-in-genome-replication-and-transcription-and-innate-immune-antagonism
#10
Watee Seesuay, Surasak Jittavisutthikul, Nawannaporn Sae-Lim, Nitat Sookrung, Yuwaporn Sakolvaree, Wanpen Chaicumpa
Small molecular inhibitors and passive immunization against Ebola virus disease (EVD) have been tested in animal models, including rodents and non-human primates, as well as in clinical trials. Nevertheless, there is currently no Food and Drug Administration (FDA)-approved therapy, and alternative strategies must be pursued. The aim of this study was to produce cell-penetrable human single-chain antibodies (transbodies) that are able to interfere with the activities of interferon inhibitory domain (IID) of the VP35 protein, a multifunctional virulence factor of Ebola virus (EBOV)...
March 21, 2018: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/29562352/structural-basis-for-leishif4e-1-modulation-by-an-interacting-protein-in-the-human-parasite-leishmania-major
#11
Shimi Meleppattu, Haribabu Arthanari, Alexandra Zinoviev, Andras Boeszoermenyi, Gerhard Wagner, Michal Shapira, Mélissa Léger-Abraham
Leishmania parasites are unicellular pathogens that are transmitted to humans through the bite of infected sandflies. Most of the regulation of their gene expression occurs post-transcriptionally, and the different patterns of gene expression required throughout the parasites' life cycle are regulated at the level of translation. Here, we report the X-ray crystal structure of the Leishmania cap-binding isoform 1, LeishIF4E-1, bound to a protein fragment of previously unknown function, Leish4E-IP1, that binds tightly to LeishIF4E-1...
March 19, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29554310/4ehp-independent-repression-of-endogenous-mrnas-by-the-rna-binding-protein-gigyf2
#12
Cinthia C Amaya Ramirez, Petra Hubbe, Nicolas Mandel, Julien Béthune
Initially identified as a factor involved in tyrosine kinase receptor signaling, Grb10-interacting GYF protein 2 (GIGYF2) has later been shown to interact with the 5' cap-binding protein 4EHP as part of a translation repression complex, and to mediate post-transcriptional repression of tethered reporter mRNAs. A current model proposes that GIGYF2 is indirectly recruited to mRNAs by specific RNA-binding proteins (RBPs) leading to translation repression through its association with 4EHP. Accordingly, we recently observed that GIGYF2 also interacts with the miRNA-induced silencing complex and probably modulates its translation repression activity...
March 15, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29545132/non-conventional-rottlerin-anticancer-properties
#13
REVIEW
E Maioli, E Daveri, E Maellaro, F Ietta, L Cresti, G Valacchi
In the past few years, we focused the interest on rottlerin, an old/new natural substance that, over the time, has revealed a number of cellular and molecular targets, all potentially implicated in the fight against cancer. Past and recent literature well demonstrated that rottlerin is an inhibitor of enzymes, transcription factors and signaling molecules that control cancer cell life and death. Although the rottlerin anticancer activity has been mainly ascribed to apoptosis and/or autophagy induction, recent findings unveiled the existence of additional mechanisms of toxicity...
May 1, 2018: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29510665/characterization-of-the-human-rfx-transcription-factor-family-by-regulatory-and-target-gene-analysis
#14
Debora Sugiaman-Trapman, Morana Vitezic, Eeva-Mari Jouhilahti, Anthony Mathelier, Gilbert Lauter, Sougat Misra, Carsten O Daub, Juha Kere, Peter Swoboda
BACKGROUND: Evolutionarily conserved RFX transcription factors (TFs) regulate their target genes through a DNA sequence motif called the X-box. Thereby they regulate cellular specialization and terminal differentiation. Here, we provide a comprehensive analysis of all the eight human RFX genes (RFX1-8), their spatial and temporal expression profiles, potential upstream regulators and target genes. RESULTS: We extracted all known human RFX1-8 gene expression profiles from the FANTOM5 database derived from transcription start site (TSS) activity as captured by Cap Analysis of Gene Expression (CAGE) technology...
March 6, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29482522/distinct-core-promoter-codes-drive-transcription-initiation-at-key-developmental-transitions-in-a-marine-chordate
#15
Gemma B Danks, Pavla Navratilova, Boris Lenhard, Eric M Thompson
BACKGROUND: Development is largely driven by transitions between transcriptional programs. The initiation of transcription at appropriate sites in the genome is a key component of this and yet few rules governing selection are known. Here, we used cap analysis of gene expression (CAGE) to generate bp-resolution maps of transcription start sites (TSSs) across the genome of Oikopleura dioica, a member of the closest living relatives to vertebrates. RESULTS: Our TSS maps revealed promoter features in common with vertebrates, as well as striking differences, and uncovered key roles for core promoter elements in the regulation of development...
February 26, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29471506/a-translational-silencing-function-of-mcpip1-regnase-1-specified-by-the-target-site-context
#16
Gesine Behrens, Reinhard Winzen, Nina Rehage, Anneke Dörrie, Monika Barsch, Anne Hoffmann, Jörg Hackermüller, Christopher Tiedje, Vigo Heissmeyer, Helmut Holtmann
The expression of proteins during inflammatory and immune reactions is coordinated by post-transcriptional mechanisms. A particularly strong suppression of protein expression is exerted by a conserved translational silencing element (TSE) identified in the 3' UTR of NFKBIZ mRNA, which is among the targets of the RNA-binding proteins Roquin-1/2 and MCPIP1/Regnase-1. We present evidence that in the context of the TSE MCPIP1, so far known for its endonuclease activity toward mRNAs specified by distinct stem-loop (SL) structures, also suppresses translation...
May 4, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29447394/human-la-binds-mrnas-through-contacts-to-the-poly-a-tail
#17
Jyotsna Vinayak, Stefano A Marrella, Rawaa H Hussain, Leonid Rozenfeld, Karine Solomon, Mark A Bayfield
In addition to a role in the processing of nascent RNA polymerase III transcripts, La proteins are also associated with promoting cap-independent translation from the internal ribosome entry sites of numerous cellular and viral coding RNAs. La binding to RNA polymerase III transcripts via their common UUU-3'OH motif is well characterized, but the mechanism of La binding to coding RNAs is poorly understood. Using electromobility shift assays and cross-linking immunoprecipitation, we show that in addition to a sequence specific UUU-3'OH binding mode, human La exhibits a sequence specific and length dependent poly(A) binding mode...
May 4, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29427323/androgen-receptor-dampens-tissue-factor-expression-via-nuclear-factor-%C3%AE%C2%BAb-and-early-growth-response-protein-1
#18
B Hoesel, M Mussbacher, B Dikorman, M Salzmann, A Assinger, L Hell, J Thaler, J Basílio, B Moser, U Resch, H Paar, N Mackman, J A Schmid
Essentials Androgen deprivation increases the rate of venous thromboembolism in prostate cancer patients. We characterized androgen receptor-mediated tissue factor regulation in prostate epithelial cells. Androgen receptor is dampening tissue factor expression in prostate epithelial cells. Androgen deprivation could enhance tissue factor expression and raise venous thromboembolism rates. SUMMARY: Background Prostate cancer is one of the leading causes of cancer death in men. Advanced prostate cancer is usually treated by androgen deprivation therapy (ADT), which is aimed at reducing circulating testosterone levels to reduce cancer growth...
April 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29339107/influenza-a-virus-polymerase-an-attractive-target-for-next-generation-anti-influenza-therapeutics
#19
REVIEW
Zhongxia Zhou, Tao Liu, Jian Zhang, Peng Zhan, Xinyong Liu
The influenza RNA-dependent RNA polymerase (RdRP) is conserved among different types of influenza virus, playing an important part in transcription and replication. In this regard, influenza RdRP is an attractive target for novel anti-influenza drug discovery. Herein, we will introduce the structural and functional information of influenza polymerase; and an overview of inhibitors targeting the PA endonuclease and PB2 cap-binding site is provided, along with the approaches utilized for identification of these inhibitors...
March 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/29298432/characterizing-zc3h18-a-multi-domain-protein-at-the-interface-of-rna-production-and-destruction-decisions
#20
Kinga Winczura, Manfred Schmid, Claudia Iasillo, Kelly R Molloy, Lea Mørch Harder, Jens S Andersen, John LaCava, Torben Heick Jensen
Nuclear RNA metabolism is influenced by protein complexes connecting to both RNA-productive and -destructive pathways. The ZC3H18 protein binds the cap-binding complex (CBC), universally present on capped RNAs, while also associating with the nuclear exosome targeting (NEXT) complex, linking to RNA decay. To dissect ZC3H18 function, we conducted interaction screening and mutagenesis of the protein, which revealed a phosphorylation-dependent isoform. Surprisingly, the modified region of ZC3H18 associates with core histone proteins...
January 2, 2018: Cell Reports
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