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https://www.readbyqxmd.com/read/27912056/conflict-resolution-in-the-genome-how-transcription-and-replication-make-it-work
#1
REVIEW
Stephan Hamperl, Karlene A Cimprich
The complex machineries involved in replication and transcription translocate along the same DNA template, often in opposing directions and at different rates. These processes routinely interfere with each other in prokaryotes, and mounting evidence now suggests that RNA polymerase complexes also encounter replication forks in higher eukaryotes. Indeed, cells rely on numerous mechanisms to avoid, tolerate, and resolve such transcription-replication conflicts, and the absence of these mechanisms can lead to catastrophic effects on genome stability and cell viability...
December 1, 2016: Cell
https://www.readbyqxmd.com/read/27909446/functional-toxicogenomic-profiling-expands-insight-into-modulators-of-formaldehyde-toxicity-in-yeast
#2
Matthew North, Brandon D Gaytán, Carlos Romero, Vanessa Y De La Rosa, Alex Loguinov, Martyn T Smith, Luoping Zhang, Chris D Vulpe
Formaldehyde (FA) is a commercially important chemical with numerous and diverse uses. Accordingly, occupational and environmental exposure to FA is prevalent worldwide. Various adverse effects, including nasopharyngeal, sinonasal, and lymphohematopoietic cancers, have been linked to FA exposure, prompting designation of FA as a human carcinogen by U.S. and international scientific entities. Although the mechanism(s) of FA toxicity have been well studied, additional insight is needed in regard to the genetic requirements for FA tolerance...
2016: Frontiers in Genetics
https://www.readbyqxmd.com/read/27909398/an-amyloid-like-pathological-conformation-of-tdp-43-is-stabilized-by-hypercooperative-hydrogen-bonds
#3
Miguel Mompeán, Marco Baralle, Emanuele Buratti, Douglas V Laurents
TDP-43 is an essential RNA-binding protein forming aggregates in almost all cases of sporadic amyotrophic lateral sclerosis (ALS) and many cases of frontotemporal lobar dementia (FTLD) and other neurodegenerative diseases. TDP-43 consists of a folded N-terminal domain with a singular structure, two RRM RNA-binding domains, and a long disordered C-terminal region which plays roles in functional RNA regulatory assemblies as well as pernicious aggregation. Evidence from pathological mutations and seeding experiments strongly suggest that TDP-43 aggregates are pathologically relevant through toxic gain-of-harmful-function and/or harmful loss-of-native-function mechanisms...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27909049/control-of-secreted-protein-gene-expression-and-the-mammalian-secretome-by-the-metabolic-regulator-pgc-1%C3%AE
#4
Neri Minsky, Robert G Roeder
Secreted proteins serve pivotal roles in the development of multicellular organisms, acting as structural matrix, extracellular enzymes and signal molecules. However, how the secretome is regulated remains incompletely understood. Here we demonstrate, unexpectedly, that peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), a critical transcriptional co-activator of metabolic gene expression, functions to down-regulate expression of diverse genes encoding secreted molecules and extracellular matrix (ECM) components to modulate the secretome...
December 1, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27908235/pentatricopeptide-motifs-in-the-n-terminal-extension-domain-of-yeast-mitochondrial-rna-polymerase-rpo41p-are-not-essential-for-its-function
#5
J Kruszewski, P Golik
The core mitochondrial RNA polymerase is a single-subunit enzyme that in yeast Saccharomyces cerevisiae is encoded by the nuclear RPO41 gene. It is an evolutionary descendant of the bacteriophage RNA polymerases, but it includes an additional unconserved N-terminal extension (NTE) domain that is unique to the organellar enzymes. This domain mediates interactions between the polymerase and accessory regulatory factors, such as yeast Sls1p and Nam1p. Previous studies demonstrated that deletion of the entire NTE domain results only in a temperature-dependent respiratory deficiency...
October 2016: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/27906161/structural-basis-for-arfa-rf2-mediated-translation-termination-on-mrnas-lacking-stop-codons
#6
Paul Huter, Claudia Müller, Bertrand Beckert, Stefan Arenz, Otto Berninghausen, Roland Beckmann, Daniel N Wilson
In bacteria, ribosomes stalled on truncated mRNAs lacking a stop codon are rescued by either the transfer-messenger RNA (tmRNA), alternative rescue factor A (ArfA) or ArfB rescue systems(1). While tmRNA- and ArfB-ribosome structures have been elucidated(2-7), structural insight into how ArfA recognizes the presence of truncated mRNAs and recruits the canonical termination release factor RF2 to rescue the stalled ribosomes is lacking. Here we present a cryo-electron microscopy reconstruction of a ribosome stalled on a truncated mRNA in the presence of ArfA and RF2...
December 1, 2016: Nature
https://www.readbyqxmd.com/read/27903913/functional-rnas-combined-assembly-and-packaging-in-vlps
#7
Po-Yu Fang, Lizzette M Gómez Ramos, Stefany Y Holguin, Chiaolong Hsiao, Jessica C Bowman, Hung-Wei Yang, Loren Dean Williams
We describe here a one pot RNA production, packaging and delivery system based on bacteriophage Qβ. We demonstrate a method for production of a novel RNAi scaffold, packaged within Qβ virus-like particles (VLPs). The RNAi scaffold is a general utility chimera that contains a functional RNA duplex with paired silencing and carrier sequences stabilized by a miR-30 stem-loop. The Qβ hairpin on the 5' end confers affinity for the Qβ coat protein (CP). Silencing sequences can include mature miRNAs and siRNAs, and can target essentially any desired mRNA...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27903899/human-mitochondrial-transcription-factors-tfam-and-tfb2m-work-synergistically-in-promoter-melting-during-transcription-initiation
#8
Aparna Ramachandran, Urmimala Basu, Shemaila Sultana, Divya Nandakumar, Smita S Patel
Human mitochondrial DNA is transcribed by POLRMT with the help of two initiation factors, TFAM and TFB2M. The current model postulates that the role of TFAM is to recruit POLRMT and TFB2M to melt the promoter. However, we show that TFAM has 'post-recruitment' roles in promoter melting and RNA synthesis, which were revealed by studying the pre-initiation steps of promoter binding, bending and melting, and abortive RNA synthesis. Our 2-aminopurine mapping studies show that the LSP (Light Strand Promoter) is melted from -4 to +1 in the open complex with all three proteins and from -4 to +3 with addition of ATP...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27901317/dendrimer-stabilized-gold-nanostars-as-a-multifunctional-theranostic-nanoplatform-for-ct-imaging-photothermal-therapy-and-gene-silencing-of-tumors
#9
Ping Wei, Jingwen Chen, Yong Hu, Xin Li, Han Wang, Mingwu Shen, Xiangyang Shi
Development of versatile nanomaterials combining diagnostic and therapeutic functionalities within one single nanoplatform is extremely important for tumor theranostics. In this work, the authors report the synthesis of a gold nanostar (Au NS)-based theranostic platform stabilized with cyclic arginine-glycine-aspartic (Arg-Gly-Asp, RGD) peptide-modified amine-terminated generation 3 poly(amidoamine) dendrimers. The formed RGD-modified dendrimer-stabilized Au NSs (RGD-Au DSNSs) are used as a gene delivery vector to complex small interfering RNA (siRNA) for computed tomography (CT) imaging, thermal imaging, photothermal therapy (PTT), and gene therapy of tumors...
November 30, 2016: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/27899930/ability-to-remove-na-and-retain-k-correlates-with-salt-tolerance-in-two-maize-inbred-lines-seedlings
#10
Yong Gao, Yi Lu, Meiqin Wu, Enxing Liang, Yan Li, Dongping Zhang, Zhitong Yin, Xiaoyun Ren, Yi Dai, Dexiang Deng, Jianmin Chen
Maize is moderately sensitive to salt stress; therefore, soil salinity is a serious threat to its production worldwide. Here, excellent salt-tolerant maize inbred line TL1317 and extremely salt-sensitive maize inbred line SL1303 were screened to understand the maize response to salt stress and its tolerance mechanisms. Relative water content, membrane stability index, stomatal conductance, chlorophyll content, maximum photochemical efficiency, photochemical efficiency, shoot and root fresh/dry weight, and proline and water soluble sugar content analyses were used to identify that the physiological effects of osmotic stress of salt stress were obvious and manifested at about 3 days after salt stress in maize...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27899666/structures-of-human-srp72-complexes-provide-insights-into-srp-rna-remodeling-and-ribosome-interaction
#11
Matthias M M Becker, Karine Lapouge, Bernd Segnitz, Klemens Wild, Irmgard Sinning
Co-translational protein targeting and membrane protein insertion is a fundamental process and depends on the signal recognition particle (SRP). In mammals, SRP is composed of the SRP RNA crucial for SRP assembly and function and six proteins. The two largest proteins SRP68 and SRP72 form a heterodimer and bind to a regulatory site of the SRP RNA. Despite their essential roles in the SRP pathway, structural information has been available only for the SRP68 RNA-binding domain (RBD). Here we present the crystal structures of the SRP68 protein-binding domain (PBD) in complex with SRP72-PBD and of the SRP72-RBD bound to the SRP S domain (SRP RNA, SRP19 and SRP68) detailing all interactions of SRP72 within SRP...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27899640/structural-insights-into-nusg-regulating-transcription-elongation
#12
Bin Liu, Thomas A Steitz
NusG is an essential transcription factor that plays multiple key regulatory roles in transcription elongation, termination and coupling translation and transcription. The core role of NusG is to enhance transcription elongation and RNA polymerase processivity. Here, we present the structure of Escherichia coli RNA polymerase complexed with NusG. The structure shows that the NusG N-terminal domain (NGN) binds at the central cleft of RNA polymerase surrounded by the β' clamp helices, the β protrusion, and the β lobe domains to close the promoter DNA binding channel and constrain the β' clamp domain, but with an orientation that is different from the one observed in the archaeal β' clamp-Spt4/5 complex...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27899597/thermotoga-maritima-nusg-domain-interaction-mediates-autoinhibition-and-thermostability
#13
Johanna Drögemüller, Christin Schneider, Kristian Schweimer, Martin Strauß, Birgitta M Wöhrl, Paul Rösch, Stefan H Knauer
NusG, the only universally conserved transcription factor, comprises an N- and a C-terminal domain (NTD, CTD) that are flexibly connected and move independently in Escherichia coli and other organisms. In NusG from the hyperthermophilic bacterium Thermotoga maritima (tmNusG), however, NTD and CTD interact tightly. This closed state stabilizes the CTD, but masks the binding sites for the interaction partners Rho, NusE and RNA polymerase (RNAP), suggesting that tmNusG is autoinhibited. Furthermore, tmNusG and some other bacterial NusGs have an additional domain, DII, of unknown function...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27895118/co-evolution-of-two-gtpases-enables-efficient-protein-targeting-in-an-rna-less-chloroplast-signal-recognition-particle-pathway
#14
Sowmya Chandrasekar, Michael J Sweredoski, Chang Ho Sohn, Sonja Hess, Shu-Ou Shan
Signal Recognition Particle (SRP) is an essential ribonucleoprotein particle that mediates the co-translational targeting of newly synthesized proteins to cellular membranes. The SRP RNA is a universally conserved component of SRP that mediates key interactions between two GTPases in SRP and its receptor, and thus enables rapid delivery of cargo to the target membrane. Notably, this essential RNA is bypassed in the chloroplast SRP (cpSRP) of green plants. Previously, we showed that the cpSRP and cpSRP receptor GTPases (cpSRP54 and cpFtsY, respectively) could interact efficiently by themselves without the SRP RNA...
November 28, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27888803/exosomal-long-noncoding-rna-crnde-h-as-a-novel-serum-based-biomarker-for-diagnosis-and-prognosis-of-colorectal-cancer
#15
Tong Liu, Xin Zhang, Shanyu Gao, Fangmiao Jing, Yongmei Yang, Lutao Du, Guixi Zheng, Peilong Li, Chen Li, Chuanxin Wang
Cancer-secreted long non-coding RNAs (lncRNAs) are emerging mediators of cancer-host cross talk. The aim of our study was to illustrate the clinical significance of the lncRNA CRNDE-h in exosomes purified from the serum of patients with colorectal cancer (CRC). The study was divided into four parts: (1) The exosome isolated methods and lncRNA detected methods which accurately and reproducibly measure CRC-related exosomal CRNDE-h in serum were optimized in preliminary pilot stage; (2) The stability of exosomal CRNDE-h was evaluated systematically; (3) The origin of exosomal CRNDE-h was explorated in vitro and in vivo; (4) The diagnostic and prognostic value of exosomal CRNDE-h for CRC were validated in 468 patients...
November 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27886048/interactions-between-the-hiv-1-unspliced-mrna-and-host-mrna-decay-machineries
#16
REVIEW
Daniela Toro-Ascuy, Bárbara Rojas-Araya, Fernando Valiente-Echeverría, Ricardo Soto-Rifo
The human immunodeficiency virus type-1 (HIV-1) unspliced transcript is used both as mRNA for the synthesis of structural proteins and as the packaged genome. Given the presence of retained introns and instability AU-rich sequences, this viral transcript is normally retained and degraded in the nucleus of host cells unless the viral protein REV is present. As such, the stability of the HIV-1 unspliced mRNA must be particularly controlled in the nucleus and the cytoplasm in order to ensure proper levels of this viral mRNA for translation and viral particle formation...
November 23, 2016: Viruses
https://www.readbyqxmd.com/read/27885761/a-stably-protonated-adenine-nucleotide-with-a-highly-shifted-pka-value-stabilizes-the-tertiary-structure-of-a-gtp-binding-rna-aptamer
#17
Antje C Wolter, A Katharina Weickhmann, Amir H Nasiri, Katharina Hantke, Oliver Ohlenschläger, Christoph H Wunderlich, Christoph Kreutz, Elke Duchardt-Ferner, Jens Wöhnert
RNA tertiary structure motifs are stabilized by a wide variety of hydrogen-bonding interactions. Protonated A and C nucleotides are normally not considered to be suitable building blocks for such motifs since their pKa values are far from physiological pH. Here, we report the NMR solution structure of an in vitro selected GTP-binding RNA aptamer bound to GTP with an intricate tertiary structure. It contains a novel kind of base quartet stabilized by a protonated A residue. Owing to its unique structural environment in the base quartet, the pKa value for the protonation of this A residue in the complex is shifted by more than 5 pH units compared to the pKa for A nucleotides in single-stranded RNA...
November 25, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27881904/long-noncoding-rnas-in-metabolic-syndrome-related-disorders
#18
REVIEW
Magdalena Losko, Jerzy Kotlinowski, Jolanta Jura
Ribonucleic acids (RNAs) are very complex and their all functions have yet to be fully clarified. Noncoding genes (noncoding RNA, sequences, and pseudogenes) comprise 67% of all genes and they are represented by housekeeping noncoding RNAs (transfer RNA (tRNA), ribosomal RNA (rRNA), small nuclear RNA (snRNA), and small nucleolar RNA (snoRNA)) that are engaged in basic cellular processes and by regulatory noncoding RNA (short and long noncoding RNA (ncRNA)) that are important for gene expression/transcript stability...
2016: Mediators of Inflammation
https://www.readbyqxmd.com/read/27881299/transient-rna-dna-hybrids-are-required-for-efficient-double-strand-break-repair
#19
Corina Ohle, Rafael Tesorero, Géza Schermann, Nikolay Dobrev, Irmgard Sinning, Tamás Fischer
RNA-DNA hybrids are a major internal cause of DNA damage within cells, and their degradation by RNase H enzymes is important for maintaining genomic stability. Here, we identified an unexpected role for RNA-DNA hybrids and RNase H enzymes in DNA repair. Using a site-specific DNA double-strand break (DSB) system in Schizosaccharomyces pombe, we showed that RNA-DNA hybrids form as part of the homologous-recombination (HR)-mediated DSB repair process and that RNase H enzymes are essential for their degradation and efficient completion of DNA repair...
November 3, 2016: Cell
https://www.readbyqxmd.com/read/27880830/synonymous-co-variation-across-the-e1-e2-gene-junction-of-hepatitis-c-virus-defines-virion-fitness
#20
Brendan A Palmer, Liam J Fanning
Hepatitis C virus is a positive-sense single-stranded RNA virus. The gene junction partitioning the viral glycoproteins E1 and E2 displays concurrent sequence evolution with the 3'-end of E1 highly conserved and the 5'-end of E2 highly heterogeneous. This gene junction is also believed to contain structured RNA elements, with a growing body of evidence suggesting that such structures can act as an additional level of viral replication and transcriptional control. We have previously used ultradeep pyrosequencing to analyze an amplicon library spanning the E1/E2 gene junction from a treatment naïve patient where samples were collected over 10 years of chronic HCV infection...
2016: PloS One
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