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https://www.readbyqxmd.com/read/28636597/phase-separation-drives-heterochromatin-domain-formation
#1
Amy R Strom, Alexander V Emelyanov, Mustafa Mir, Dmitry V Fyodorov, Xavier Darzacq, Gary H Karpen
Constitutive heterochromatin is an important component of eukaryotic genomes that has essential roles in nuclear architecture, DNA repair and genome stability, and silencing of transposon and gene expression. Heterochromatin is highly enriched for repetitive sequences, and is defined epigenetically by methylation of histone H3 at lysine 9 and recruitment of its binding partner heterochromatin protein 1 (HP1). A prevalent view of heterochromatic silencing is that these and associated factors lead to chromatin compaction, resulting in steric exclusion of regulatory proteins such as RNA polymerase from the underlying DNA...
June 21, 2017: Nature
https://www.readbyqxmd.com/read/28636339/binding-differences-of-two-homochiral-ru-bpy-2dppz-2-complexes-with-poly-u-%C3%A2-poly-a-poly-u-triplex-rna
#2
Meng-Na Peng, Zhi-Yuan Zhu, Li-Feng Tan
The first investigation of chiral ruthenium(II) complexes Δ- and Λ-[Ru(bpy)2dppz](2+) and triplex RNA poly(U)·poly(A)*poly(U) was carried out, which showed that Δ enantiomer displayed significant ability in stabilizing model triplex RNA.
June 21, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28633417/polypyrimidine-tract-binding-protein-ptb-and-ptb-associated-splicing-factor-in-cvb3-infection-an-itaf-for-an-itaf
#3
Pratik Dave, Biju George, Divya Khandige Sharma, Saumitra Das
The 5΄ UTR of Coxsackievirus B3 (CVB3) contains internal ribosome entry site (IRES), which allows cap-independent translation of the viral RNA and a 5΄-terminal cloverleaf structure that regulates viral replication, translation and stability. Here, we demonstrate that host protein PSF (PTB associated splicing factor) interacts with the cloverleaf RNA as well as the IRES element. PSF was found to be an important IRES trans acting factor (ITAF) for efficient translation of CVB3 RNA. Interestingly, cytoplasmic abundance of PSF protein increased during CVB3 infection and this is regulated by phosphorylation status at two different amino acid positions...
June 15, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28630140/three-dimensional-structure-of-the-3-x-tail-of-hepatitis-c-virus-rna-in-monomeric-and-dimeric-states
#4
Angel Cantero-Camacho, Lixin Fan, Yun-Xing Wang, José Gallego
The 3'X domain is a 98-nucleotide region located at the 3' end of hepatitis C virus genomic RNA that plays essential functions in the viral life cycle. It contains an absolutely conserved, 16-base palindromic sequence that promotes viral RNA dimerization, overlapped with a 7-nucleotide tract implicated in a distal contact with a nearby functional sequence. Using small angle X-ray scattering measurements combined with model building guided by NMR spectroscopy, we have studied the stoichiometry, structure and flexibility of domain 3'X and two smaller subdomain sequences as a function of ionic strength, and obtained a three-dimensional view of the full-length domain in its monomeric and dimeric states...
June 19, 2017: RNA
https://www.readbyqxmd.com/read/28625896/lateralization-of-housekeeping-genes-in-the-brain-of-one-day-old-chicks
#5
Jacek Lenart, Klaudia Kogut, Elzbieta Salinska
Real-time quantitative PCR is an exceptionally sensitive method that can detect even very small differences in gene expression and, as such, it is essential to use suitable reference genes. Domestic chickens are used in a wide range of studies including neurobiology, behavior, ecology and disease transmission. In recent avian gene expression experiments, 18S (18S ribosomal RNA), beta actin (ACTB) and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) have frequently been used; however, there is not enough evidence that these reference genes are suitable for all types of experiments...
June 15, 2017: Gene Expression Patterns: GEP
https://www.readbyqxmd.com/read/28625393/establishment-and-characterization-of-uterine-sarcoma-and-carcinosarcoma-patient-derived-xenograft-models
#6
Tine Cuppens, Jeroen Depreeuw, Daniela Annibali, Debby Thomas, Els Hermans, Ellen Gommé, Xuan Bich Trinh, David Debruyne, Philippe Moerman, Diether Lambrechts, Frédéric Amant
OBJECTIVE: Uterine sarcomas (US) and carcinosarcomas (CS) are rare, aggressive cancers. The lack of reliable preclinical models hampers the search for new treatment strategies and predictive biomarkers. To this end, we established and characterized US and CS patient-derived xenograft (PDX) models. METHODS: Tumor fragments of US and CS were subcutaneously implanted into immunocompromised mice. Engrafted xenograft and original tumors were compared by means of histology, immunohistochemistry, whole-genome low-coverage sequencing for copy number variations, and RNA sequencing...
June 16, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28625270/-progress-in-relationship-of-the-long-non-coding-rna-and-sepsis
#7
Lingling Sun, Li Li, Jing Yan
The mechanism of long chain non-coding RNA (lncRNA) is diverse. LncRNA can regulate the expression of genes at multiple levels and is closely related to some pathological process, such as tumor formation, viral replication, inflammatory damage, etc. The abnormal expression of lncRNA is involved in the patho-physiological changes of the disease, and plays a key role in many links, such as the stability of mRNA, the regulation of translation level, protein transport, RNA processing and modification, and so on...
February 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28624538/analysis-of-mrna-deadenylation-by-multi-protein-complexes
#8
Michael W Webster, James A W Stowell, Terence T L Tang, Lori A Passmore
Poly(A) tails are found at the 3' end of almost every eukaryotic mRNA and are important for the stability of mRNAs and their translation into proteins. Thus, removal of the poly(A) tail, a process called deadenylation, is critical for regulation of gene expression. Most deadenylation enzymes are components of large multi-protein complexes. Here, we describe an in vitro deadenylation assay developed to study the exonucleolytic activities of the multi-protein Ccr4-Not and Pan2-Pan3 complexes. We discuss how this assay can be used with short synthetic RNAs, as well as longer RNA substrates generated using in vitro transcription...
June 13, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28624192/stimuli-responsive-mesoporous-silica-nps-as-non-viral-dual-sirna-chemotherapy-carriers-for-triple-negative-breast-cancer
#9
REVIEW
Behrad Darvishi, Leila Farahmand, Keivan Majidzadeh-A
Triple negative breast cancer (TNBC) is the most aggressive and lethal subtype of breast cancer. It is associated with a very poor prognosis and intrinsically resistant to several conventional and targeted chemotherapy agents and has a 5-year survival rate of less than 25%. Because the treatment options for TNBC are very limited and not efficient enough for achieving minimum desired goals, shifting toward a new generation of anti-cancer agents appears to be very critical. Among recent alternative approaches being proposed, small interfering RNA (siRNA) gene therapy can potently suppress Bcl-2 proto-oncogene and p-glycoprotein gene expression, the most important chemotherapy resistance inducers in TNBC...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28624185/the-formation-of-nanoparticles-between-small-interfering-rna-and-amphipathic-cell-penetrating-peptides
#10
Ly Pärnaste, Piret Arukuusk, Kent Langel, Tanel Tenson, Ülo Langel
Cell-penetrating peptides (CPPs) are delivery vectors widely used to aid the transport of biologically active cargoes to intracellular targets. These cargoes include small interfering RNAs (siRNA) that are not naturally internalized by cells. Elucidating the complexities behind the formation of CPP and cargo complexes is crucial for understanding the processes related to their delivery. In this study, we used modified analogs of the CPP transportan10 and investigated the binding properties of these CPPs to siRNA, the formation parameters of the CPP/siRNA complexes, and their stabiliy to enzymatic degradation...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28623663/structural-mechanism-of-atp-independent-transcription-initiation-by-rna-polymerase-i
#11
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/28622299/a-circular-rna-promotes-tumorigenesis-by-inducing-c-myc-nuclear-translocation
#12
Qi Yang, William W Du, Nan Wu, Weining Yang, Faryal Mehwish Awan, Ling Fang, Jian Ma, Xiangmin Li, Yan Zeng, Zhenguo Yang, Jun Dong, Azam Khorshidi, Burton B Yang
Circular RNAs (circRNAs) are a subclass of noncoding RNAs widely expressed in mammalian cells. We report here the tumorigenic capacity of a circRNA derived from angiomotin-like1 (circ-Amotl1). Circ-Amotl1 is highly expressed in patient tumor samples and cancer cell lines. Single-cell inoculations using circ-Amotl1-transfected tumor cells showed a 30-fold increase in proliferative capacity relative to control. Agarose colony-formation assays similarly revealed a 142-fold increase. Tumor-take rate in nude mouse xenografts using 6-day (219 cells) and 3-day (9 cells) colonies were 100%, suggesting tumor-forming potential of every cell...
June 16, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28621755/biophysical-mode-of-action-and-selectivity-analysis-of-allosteric-inhibitors-of-hepatitis-c-virus-hcv-polymerase
#13
Eldar Abdurakhmanov, Sara Øie Solbak, U Helena Danielson
Allosteric inhibitors of hepatitis C virus (HCV) non-structural protein 5B (NS5B) polymerase are effective for treatment of genotype 1, although their mode of action and potential to inhibit other isolates and genotypes are not well established. We have used biophysical techniques and a novel biosensor-based real-time polymerase assay to investigate the mode-of-action and selectivity of four inhibitors against enzyme from genotypes 1b (BK and Con1) and 3a. Two thumb inhibitors (lomibuvir and filibuvir) interacted with all three NS5B variants, although the affinities for the 3a enzyme were low...
June 16, 2017: Viruses
https://www.readbyqxmd.com/read/28621679/circular-rnas-a-novel-type-of-biomarker-and-genetic-tools-in-cancer
#14
REVIEW
Yi-Neng Han, Sheng-Qiang Xia, Yuan-Yuan Zhang, Jun-Hua Zheng, Wei Li
Circular RNAs (circRNAs) are a novel type of universal and diverse endogenous noncoding RNAs (ncRNAs) and they form a covalently closed continuous loop without 5' or 3' tails unlike linear RNAs. Most circRNAs are presented with characteristics of abundance, stability, conservatism, and often exhibiting tissue/developmental-stage-specific expression. CircRNAs are generated either from exons or introns by back splicing or lariat introns. CircRNAs play important roles as miRNA sponges, gene transcription and expression regulators, RNA-binding protein (RBP) sponges and protein/peptide translators...
June 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28618265/making-the-mark-the-role-of-adenosine-modifications-in-the-life-cycle-of-rna-viruses
#15
REVIEW
Sarah R Gonzales-van Horn, Peter Sarnow
Viral epitranscriptomics is a newly emerging field that has identified unique roles for RNA modifications in modulating life cycles of RNA viruses. Despite the observation of a handful of modified viral RNAs five decades ago, very little was known about how these modifications regulate viral life cycles, until recently. Here we review the pro- and anti-viral effects of methyl-6-adenosine in distinct viral life cycles, the role of 2' O-methyl modifications in RNA stability and innate immune sensing, and functions of adenosine to inosine modifications in retroviral life cycles...
June 14, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28617612/effect-of-urea-on-g-quadruplex-stability
#16
Lusine Aslanyan, Jordan Ko, Byul G Kim, Ishkhan Vardanyan, Yeva B Dalyan, Tigran V Chalikian
G-quadruplexes represent a class of noncanonical nucleic acid structures implicated in transcriptional regulation, cellular function, and disease. An understanding of the forces involved in stabilization/destabilization of the G-quadruplex conformation relative to the duplex or single-stranded conformation is a key to elucidating the biological role of G-quadruplex-based genomic switches and the quest for therapeutic means for controlled induction or suppression of a G-quadruplex at selected genomic loci. Solute-solvent interactions provide a ubiquitous and, in many cases, the determining thermodynamic force in maintaining and modulating the stability of nucleic acids...
June 15, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28617590/structure-and-dynamics-of-rna-repeat-expansions-that-cause-huntington-s-disease-and-myotonic-dystrophy-type-1
#17
Jonathan L Chen, Damian M VanEtten, Matthew A Fountain, Ilyas Yildirim, Matthew D Disney
RNA repeat expansions cause a host of incurable, genetically-defined diseases. The most common class of RNA repeats are trinucleotide repeats. These long, repeating transcripts fold into hairpins containing 1 × 1 internal loops that can mediate disease via a variety of mechanism(s) in which RNA is the central player. Two of these disorders are Huntington's disease and myotonic dystrophy type 1, which are caused by r(CAG) and r(CUG) repeats, respectively. We report the structures of two RNA constructs containing three copies of a r(CAG) [r(3×CAG)] or r(CUG) [r(3×CUG)] motif that were modeled with nuclear magnetic resonance spectroscopy and simulated annealing with restrained molecular dynamics...
June 15, 2017: Biochemistry
https://www.readbyqxmd.com/read/28617439/cdc20-directs-proteasome-mediated-degradation-of-the-tumor-suppressor-smar1-in-higher-grades-of-cancer-through-the-anaphase-promoting-complex
#18
Debasish Paul, Suvankar Ghorai, U S Dinesh, Praveenkumar Shetty, Samit Chattopadhyay, Manas Kumar Santra
The Tumor suppressor SMAR1 (scaffold matrix attachment region binding protein 1) has a crucial role in maintaining genomic stability, cell cycle progression and apoptosis.Our previous finding showed that it is highly suppressed in higher grade of cancer. However, the underlying mechanism of this suppression was not well understood. In this study, we show that SMAR1 expression levels are controlled at the proteasomal level by five RING finger E3 ubiquitin ligases including, Cdc20, a substrate receptor of ubiquitin ligase APC/C complex...
June 15, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28615029/micrornas-control-mrna-fate-by-compartmentalization-based-on-3-utr-length-in-male-germ-cells
#19
Ying Zhang, Chong Tang, Tian Yu, Ruirui Zhang, Huili Zheng, Wei Yan
BACKGROUND: Post-transcriptional regulation of gene expression can be achieved through the control of mRNA stability, cytoplasmic compartmentalization, 3' UTR length and translational efficacy. Spermiogenesis, a process through which haploid male germ cells differentiate into spermatozoa, represents an ideal model for studying post-transcriptional regulation in vivo because it involves a large number of transcripts that are physically sequestered in ribonucleoprotein particles (RNPs) and thus subjected to delayed translation...
June 15, 2017: Genome Biology
https://www.readbyqxmd.com/read/28614747/rna-mediated-regulation-of-heterochromatin
#20
REVIEW
Whitney L Johnson, Aaron F Straight
The formation of condensed, transcriptionally repressed heterochromatin is essential for controlling gene expression throughout development, silencing parasitic DNA elements, and for genome stability and inheritance. Cells employ diverse mechanisms for controlling heterochromatin states through proteins that modify DNA and histones. An emerging theme is that chromatin-associated RNAs play important roles in regulating heterochromatin proteins by controlling their initial recruitment to chromatin, their stable association with chromatin, their spread along chromatin, or their enzymatic activity...
June 11, 2017: Current Opinion in Cell Biology
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