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RNA Polymerase II

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https://www.readbyqxmd.com/read/28640868/functional-metabolomics-as-a-tool-to-analyze-mediator-function-and-structure-in-plants
#1
Celine Davoine, Ilka N Abreu, Khalil Khajeh, Jeanette Blomberg, Brendan N Kidd, Kemal Kazan, Peer M Schenk, Lorenz Gerber, Ove Nilsson, Thomas Moritz, Stefan Björklund
Mediator is a multiprotein transcriptional co-regulator complex composed of four modules; Head, Middle, Tail, and Kinase. It conveys signals from promoter-bound transcriptional regulators to RNA polymerase II and thus plays an essential role in eukaryotic gene regulation. We describe subunit localization and activities of Mediator in Arabidopsis through metabolome and transcriptome analyses from a set of Mediator mutants. Functional metabolomic analysis based on the metabolite profiles of Mediator mutants using multivariate statistical analysis and heat-map visualization shows that different subunit mutants display distinct metabolite profiles, which cluster according to the reported localization of the corresponding subunits in yeast...
2017: PloS One
https://www.readbyqxmd.com/read/28637276/repetitive-element-transcripts-are-elevated-in-the-brain-of-c9orf72-als-ftld-patients
#2
Mercedes Prudencio, Patrick K Gonzales, Casey N Cook, Tania F Gendron, Lillian M Daughrity, Yuping Song, Mark T W Ebbert, Marka van Blitterswijk, Yong-Jie Zhang, Karen Jansen-West, Matthew C Baker, Michael DeTure, Rosa Rademakers, Kevin B Boylan, Dennis W Dickson, Leonard Petrucelli, Christopher D Link
Significant transcriptome alterations are detected in the brain of patients with amyotrophic lateral sclerosis (ALS), including carriers of the C9orf72 repeat expansion and C9orf72-negative sporadic cases. Recently, the expression of repetitive element transcripts has been associated with toxicity and, while increased repetitive element expression has been observed in several neurodegenerative diseases, little is known about their contribution to ALS. To assess whether aberrant expression of repetitive element sequences are observed in ALS, we analyzed RNA sequencing data from C9orf72-positive and sporadic ALS cases, as well as healthy controls...
June 16, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28636937/the-conserved-rna-binding-cyclophilin-rct1-regulates-small-rna-biogenesis-and-splicing-independent-of-heterochromatin-assembly
#3
An-Yun Chang, Stephane E Castel, Evan Ernst, Hyun Soo Kim, Robert A Martienssen
RNAi factors and their catalytic activities are essential for heterochromatin assembly in S. pombe. This has led to the idea that siRNAs can promote H3K9 methylation by recruiting the cryptic loci regulator complex (CLRC), also known as recombination in K complex (RIKC), to the nucleation site. The conserved RNA-binding protein Rct1 (AtCyp59/SIG-7) interacts with splicing factors and RNA polymerase II. Here we show that Rct1 promotes processing of pericentromeric transcripts into siRNAs via the RNA recognition motif...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28633434/psip1-p75-promotes-tumorigenicity-in-breast-cancer-cells-by-promoting-the-transcription-of-cell-cycle-genes
#4
Deepak K Singh, Omid Gholamalamdari, Mahdieh Jadaliha, Xiao Ling Li, Yo-Chuen Lin, Yang Zhang, Shuomeng Guang, Seyedsasan Hashemikhabir, Saumya Tiwari, Yuelin J Zhu, Abid Khan, Anu Thomas, Arindam Chakraborty, Virgilia Macias, Andre K Balla, Rohit Bhargava, Sarath Chandra Janga, Jian Ma, Supriya G Prasanth, Ashish Lal, Kannanganattu V Prasanth
Breast cancer (BC) is a highly heterogeneous disease, both at the pathological and molecular level, and several chromatin-associated proteins play crucial roles in breast cancer initiation and progression. Here, we demonstrate the role of PSIP1 (PC4 and SF2 interacting protein)/p75 (LEDGF) in breast cancer progression. PSIP1/p75, previously identified as a chromatin-adaptor protein, is found to be upregulated in basal-like/triple negative breast cancer (TNBC) patient samples and cell lines. Immunohistochemistry in tissue arrays showed elevated levels of PSIP1 in metastatic invasive ductal carcinoma...
June 17, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28631286/knockdown-of-mediator-subunit-med19-suppresses-bladder-cancer-cell-proliferation-and-migration-by-downregulating-wnt-%C3%AE-catenin-signalling-pathway
#5
Hejia Yuan, Shengqiang Yu, Yuanshan Cui, Changping Men, Diandong Yang, Zhenli Gao, Zhe Zhu, Jitao Wu
Mediator complex subunit 19 (Med19), a RNA polymerase II-embedded coactivator, is reported to be involved in bladder cancer (BCa) progression, but its functional contribution to this process is poorly understood. Here, we investigate the effects of Med19 on malignant behaviours of BCa, as well as to elucidate the possible mechanisms. Med19 expression in 15 BCa tissues was significantly higher than adjacent paired normal tissues using real-time PCR and Western blot analysis. Immunohistochemical staining of 167 paraffin-embedded BCa tissues was performed, and the results showed that high Med19 protein level was positively correlated with clinical stages and histopathological grade...
June 19, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28628097/cpf1-proteins-excise-crispr-rnas-from-mrna-transcripts-in-mammalian-cells
#6
Guocai Zhong, Haimin Wang, Yujun Li, Mai H Tran, Michael Farzan
Cpf1 is a CRISPR effector protein that has greater specificity than Streptococcus pyogenes Cas9 (SpCas9) in genome-editing applications. Here we show that Lachnospiraceae bacterium (Lb) and Acidaminococus sp. (As) Cpf1 orthologs have RNase activities that can excise multiple CRISPR RNAs (crRNAs) from a single RNA polymerase II-driven RNA transcript expressed in mammalian cells. This property simplifies modification of multiple genomic targets and can be used to increase the efficiency of Cpf1-mediated editing...
June 19, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28625977/p300-mediated-acetylation-of-the-notch-effector-transcription-factor-maml-1-recruits-nack-to-initiate-notch-dependent-transcription
#7
Ke Jin, Wen Zhou, Xiaoqing Han, Zhiqiang Wang, Bin Li, Shawn Jeffries, Wensi Tao, David J Robbins, Anthony J Capobianco
Although it has long been appreciated that p300 acts as a critical Notch coactivator, the mechanistic details of p300 in Notch-mediated transcription remain unclear. We previously demonstrated that PEAK1-related kinase activating pseudokinase 1 (NACK) is a critical co-activator of Notch signaling and binds to the Notch1 ternary complex. Herein we report that p300 and CBP acetylate mastermind-like transcriptional coactivator 1 (Maml1) on amino acid residues K188 and K189 to recruit NACK to the Notch1 ternary complex, which results in the recruitment of RNA polymerase II to initiate transcription...
June 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28623663/structural-mechanism-of-atp-independent-transcription-initiation-by-rna-polymerase-i
#8
Yan Han, Chunli Yan, Thi Hoang Duong Nguyen, Ashleigh J Jackobel, Ivaylo Ivanov, Bruce A Knutson, Yuan He
Transcription initiation by RNA Polymerase I (Pol I) depends on the Core Factor (CF) complex to recognize the upstream promoter and assemble into a Pre-Initiation Complex (PIC). Here, we solve a structure of Saccharomyces cerevisiae Pol I-CF-DNA to 3.8Å resolution using single-particle cryo-electron microscopy. The structure reveals a bipartite architecture of Core Factor and its recognition of the promoter from -27 to -16. Core Factor's intrinsic mobility correlates well with different conformational states of the Pol I cleft, in addition to the stabilization of either Rrn7 N-terminal domain near Pol I wall or the tandem winged helix domain of A49 at a partially overlapping location...
June 17, 2017: ELife
https://www.readbyqxmd.com/read/28623583/characterization-of-mediator-complex-and-its-associated-proteins-from-rice
#9
Subhasis Samanta, Jitendra Kumar Thakur
The Mediator complex is a multi-protein complex that acts as a molecular bridge conveying transcriptional messages from the cis element-bound transcription factor to the RNA Polymerase II machinery. It is found in all eukaryotes including members of the plant kingdom. Increasing number of reports from plants regarding different Mediator subunits involved in a multitude of processes spanning from plant development to environmental interactions have firmly established it as a central hub of plant regulatory networks...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28622431/loss-of-cdkc-2-increases-both-cell-division-and-drought-tolerance-in-arabidopsis-thaliana
#10
Lina Zhao, Yaqiong Li, Qi Xie, Yaorong Wu
Drought stress is one of abiotic stresses limiting plant growth and agricultural productivity. To further understand the mechanism of drought tolerance and identify the genes involved in this process, a genetic screen for altered drought response was conducted in Arabidopsis. One mutant with enhanced drought tolerance was isolated and named atdtm1 (Arabidopsis drought tolerance mutant 1), which has larger lateral organs, prolonged growth duration, increased relative water content and a reduced leaf stomatal density compared with the wild type...
June 16, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28621907/role-of-cleavage-and-polyadenylation-specificity-factor-100-anchoring-poly-a-sites-and-modulating-transcription-termination
#11
Juncheng Lin, Ruqiang Xu, Xiaohui Wu, Yingjia Shen, Qingshun Q Li
CPSF100 is a core component of the Cleavage and Polyadenylation Specificity Factor (CPSF) complex for the 3'-end formation of mRNA, but it still has no clear functional assignment. CPSF100 was reported to play a role in RNA silencing and promote flowering in Arabidopsis. However, the molecular mechanisms underlying these phenomena are not fully understood. Our genetics analyses indicate that plants with a hypomorphic mutant of CPSF100 (esp5) show defects in embryogenesis, reduced seed production, or altered root morphology...
June 16, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28615474/regulation-of-expression-of-human-rna-polymerase-ii-transcribed-snrna-genes
#12
REVIEW
Joana Guiro, Shona Murphy
In addition to protein-coding genes, RNA polymerase II (pol II) transcribes numerous genes for non-coding RNAs, including the small-nuclear (sn)RNA genes. snRNAs are an important class of non-coding RNAs, several of which are involved in pre-mRNA splicing. The molecular mechanisms underlying expression of human pol II-transcribed snRNA genes are less well characterized than for protein-coding genes and there are important differences in expression of these two gene types. Here, we review the DNA features and proteins required for efficient transcription of snRNA genes and co-transcriptional 3' end formation of the transcripts...
June 2017: Open Biology
https://www.readbyqxmd.com/read/28611663/epigenetic-modifications-to-h3k9-in-renal-tubulointerstitial-cells-after-unilateral-ureteric-obstruction-and-tgf-%C3%AE-1-stimulation
#13
Timothy D Hewitson, Stephen G Holt, Sven-Jean Tan, Belinda Wigg, Chrishan S Samuel, Edward R Smith
Introduction: Epigenetic regulation of fibrogenesis through post-translational histone modifications (marks) may be a key determinant of progression in renal disease. In this study, we examined the distribution and acquisition of histone 3 Lysine 9 (H3K9) marks after injury and stimulation with the pro-fibrotic cytokine TGF-β1. Our focus was on their presence in activated fibroblasts (myofibroblasts) and epithelial cells (epithelial-mesenchymal transition). Methods and Results: Immunofluorescent microscopy was used to examine global H3K9 acetylation (H3K9Ac) and tri-methylation (H3K9Me3) after unilateral ureteric obstruction (UUO) in mice...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28611293/identification-of-molecular-biomarkers-for-pancreatic-cancer-with-mrmr-shortest-path-method
#14
Shuhua Shen, Tuantuan Gui, Chengcheng Ma
The high mortality rate of pancreatic cancer makes it one of the most studied diseases among all cancer types. Many researches have been conducted to understand the mechanism underlying its emergence and pathogenesis of this disease. Here, by using minimum-redundancy-maximum-relevance (mRMR) method, we studied a set of transcriptome data of pancreatic cancer. As we gradually added features to achieve the most accurate classification results of Jackknife, a gene set of 9 genes was identified. They were NHS, SCML2, LAMC2, S100P, COL17A1, AMIGO2, PTPRR, KPNA7 and KCNN4...
June 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28611249/a-herpesviral-immediate-early-protein-promotes-transcription-elongation-of-viral-transcripts
#15
Hannah L Fox, Jill A Dembowski, Neal A DeLuca
Herpes simplex virus 1 (HSV-1) genes are transcribed by cellular RNA polymerase II (RNA Pol II). While four viral immediate early proteins (ICP4, ICP0, ICP27, and ICP22) function in some capacity in viral transcription, the mechanism by which ICP22 functions remains unclear. We observed that the FACT complex (comprised of SSRP1 and Spt16) was relocalized in infected cells as a function of ICP22. ICP22 was also required for the association of FACT and the transcription elongation factors SPT5 and SPT6 with viral genomes...
June 13, 2017: MBio
https://www.readbyqxmd.com/read/28607146/epigenetic-transcriptional-memory-of-gal-genes-depends-on-growth-in-glucose-and-the-tup1-transcription-factor-in-saccharomyces-cerevisiae
#16
Varun Sood, Ivelisse Cajigas, Agustina D'Urso, William H Light, Jason H Brickner
Previously expressed inducible genes can remain poised for faster reactivation for multiple cell divisions, a conserved phenomenon called epigenetic transcriptional memory. The GAL genes in Saccharomyces cerevisiae show faster reactivation for up to seven generations after being repressed. During memory, previously produced Gal1 protein enhances the rate of reactivation of GAL1, GAL10, GAL2 and GAL7 These genes also interact with the nuclear pore complex (NPC) and localize to the nuclear periphery both when active and during memory...
June 12, 2017: Genetics
https://www.readbyqxmd.com/read/28603751/production-of-guide-rnas-in-vitro-and-in-vivo-for-crispr-using-ribozymes-and-rna-polymerase-ii-promoters
#17
Tao Zhang, Yangbin Gao, Rongchen Wang, Yunde Zhao
CRISPR/Cas9-mediated genome editing relies on a guide RNA (gRNA) molecule to generate sequence-specific DNA cleavage, which is a prerequisite for gene editing. Here we establish a method that enables production of gRNAs from any promoters, in any organisms, and in vitro (Gao and Zhao, 2014). This method also makes it feasible to conduct tissue/cell specific gene editing.
February 20, 2017: Bio-protocol
https://www.readbyqxmd.com/read/28603670/the-nematode-homologue-of-mediator-complex-subunit-28-f28f8-5-is-a-critical-regulator-of-c-elegans-development
#18
Markéta Kostrouchová, David Kostrouch, Ahmed A Chughtai, Filip Kaššák, Jan P Novotný, Veronika Kostrouchová, Aleš Benda, Michael W Krause, Vladimír Saudek, Marta Kostrouchová, Zdeněk Kostrouch
The evolutionarily conserved Mediator complex is a critical player in regulating transcription. Comprised of approximately two dozen proteins, the Mediator integrates diverse regulatory signals through direct protein-protein interactions that, in turn, modulate the influence of Mediator on RNA Polymerase II activity. One Mediator subunit, MED28, is known to interact with cytoplasmic structural proteins, providing a potential direct link between cytoplasmic dynamics and the control of gene transcription. Although identified in many animals and plants, MED28 is not present in yeast; no bona fide MED28 has been described previously in Caenorhabditis elegans...
2017: PeerJ
https://www.readbyqxmd.com/read/28598254/archaeal-rna-polymerase-arrests-transcription-at-dna-lesions
#19
Alexandra M Gehring, Thomas J Santangelo
Transcription elongation is not uniform and transcription is often hindered by protein-bound factors or DNA lesions that limit translocation and impair catalysis. Despite the high degree of sequence and structural homology of the multi-subunit RNAPs, substantial differences in response to DNA lesions have been reported. Archaea encode only a single RNAP with striking structural conservation with eukaryotic RNAP II (Pol II). Here we demonstrate that the archaeal RNAP from Thermococcus kodakarensis is sensitive to a variety of DNA lesions that pause and arrest RNAP at or adjacent to the site of DNA damage...
June 9, 2017: Transcription
https://www.readbyqxmd.com/read/28592488/dna-damage-induced-atr-kinase-activation-in-non-replicating-cells-is-regulated-by-the-xpb-subunit-of-transcription-factor-ii-h-tfiih
#20
Michael G Kemp
The role of the DNA damage response protein kinase ataxia telangiectasia and Rad-3-related (ATR) in the cellular response to DNA damage during the replicative phase of the cell cycle has been extensively studied. However, little is known about ATR kinase function in cells that are not actively replicating DNA and which constitute most cells in the human body. Using small-molecule inhibitors of ATR kinase and overexpression of a kinase-inactive form of the enzyme, I show here that ATR promotes cell death in non-replicating/non-cycling cultured human cells exposed to N-acetoxy-2-acetylaminofluorene (NA-AAF), which generates bulky DNA adducts that block RNA polymerase movement...
June 7, 2017: Journal of Biological Chemistry
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