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https://www.readbyqxmd.com/read/29458129/honeysuckle-encoded-microrna2911-inhibits-enterovirus-71-replication-via-targeting-vp1-gene
#1
Xihan Li, Ying Huang, Menghuai Sun, Hong Ji, Hui Dou, Jia Hu, Yanfeng Yan, Xu Wang, Leiyao Chen
Enterovirus 71 (EV71) is the primary pathogen of hand-foot-and-mouth disease (HFMD) in children and virus infections are associated with severe neurological dysfunctions and even death. MIR2911 is a honeysuckle-encoded atypical microRNA with extremely stability. Here, we report that MIR2911 directly inhibits EV71 replication by targeting the VP1 gene. Bioinformatics prediction and luciferase reporter assay showed that MIR2911 could target the VP1 gene of EV71. Transfection experiments using synthetic MIR2911 and extracted RNA from HS decoction shown that each of these preparations was capable of inhibiting EV71 VP1 protein expression; however, these preparations did not impact EV71 mutants in which the MIR2911-binding sites were mutated...
February 16, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29456882/effects-of-osmolytes-and-macromolecular-crowders-on-stable-gaaa-tetraloops-and-their-preference-for-a-cg-closing-base-pair
#2
Kaethe N Leonard, Joshua M Blose
Osmolytes and macromolecular crowders have the potential to influence the stability of secondary structure motifs and alter preferences for conserved nucleic acid sequences in vivo . To further understand the cellular function of RNA we observed the effects of a model osmolyte, polyethylene glycol (PEG) 200, and a model macromolecular crowding agent, PEG 8000, on the GAAA tetraloop motif. GAAA tetraloops are conserved, stable tetraloops, and are critical participants in RNA tertiary structure. They also have a thermodynamic preference for a CG closing base pair...
2018: PeerJ
https://www.readbyqxmd.com/read/29456020/advanced-sirna-designs-further-improve-in-vivo-performance-of-galnac-sirna-conjugates
#3
Donald J Foster, Christopher R Brown, Sarfraz Shaikh, Casey Trapp, Mark K Schlegel, Kun Qian, Alfica Sehgal, Kallanthottathil G Rajeev, Vasant Jadhav, Muthiah Manoharan, Satya Kuchimanchi, Martin A Maier, Stuart Milstein
Significant progress has been made in the advancement of RNAi therapeutics by combining a synthetic triantennary N-acetylgalactosamine ligand targeting the asialoglycoprotein receptor with chemically modified small interfering RNA (siRNA) designs, including the recently described Enhanced Stabilization Chemistry. This strategy has demonstrated robust RNAi-mediated gene silencing in liver after subcutaneous administration across species, including human. Here we demonstrate that substantial efficacy improvements can be achieved through further refinement of siRNA chemistry, optimizing the positioning of 2'-deoxy-2'-fluoro and 2'-O-methyl ribosugar modifications across both strands of the double-stranded siRNA duplex to enhance stability without compromising intrinsic RNAi activity...
January 4, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29454929/hur-mediated-scn5a-mrna-stability-reduces-arrhythmic-risk-in-heart-failure
#4
Anyu Zhou, An Xie, Tae Yun Kim, Hong Liu, Guangbin Shi, Gyeoung-Jin Kang, Ning Jiang, Man Liu, Euy-Myoung Jeong, Bum-Rak Choi, Samuel C Dudley
BACKGROUND: Downregulated sodium currents in heart failure (HF) has been linked to increased arrhythmic risk. Reduced expression of mRNA stabilizing protein ELAVL1/HuR may be responsible for the downregulation of sodium channel gene SCN5A mRNA. OBJECTIVE: To investigate whether HuR regulates SCN5A mRNA expression and whether manipulation of HuR benefits arrhythmia control in HF. METHODS: Quantitative real-time reverse-transcriptase PCR (qRT-PCR) were used to investigate the expression of SCN5A...
February 15, 2018: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/29454463/a-review-on-cationic-lipids-with-different-linkers-for-gene-delivery
#5
REVIEW
Defu Zhi, Yuchao Bai, Jian Yang, Shaohui Cui, Yinan Zhao, Huiying Chen, Shubiao Zhang
Cationic lipids have become known as one of the most versatile tools for the delivery of DNA, RNA and many other therapeutic molecules, and are especially attractive because they can be easily designed, synthesized and characterized. Most of cationic lipids share the common structure of cationic head groups and hydrophobic portions with linker bonds between both domains. The linker bond is an important determinant of the chemical stability and biodegradability of cationic lipid, and further governs its transfection efficiency and cytotoxicity...
December 26, 2017: Advances in Colloid and Interface Science
https://www.readbyqxmd.com/read/29453323/rna-stabilization-factors-in-chloroplasts-of-vascular-plants
#6
REVIEW
Nikolay Manavski, Lisa-Marie Schmid, Jörg Meurer
In contrast to the cyanobacterial ancestor, chloroplast gene expression is predominantly governed on the post-transcriptional level such as modifications of the RNA sequence, decay rates, exo- and endonucleolytic processing as well as translational events. The concerted function of numerous chloroplast RNA-binding proteins plays a fundamental and often essential role in all these processes but our understanding of their impact in regulation of RNA degradation is only at the beginning. Moreover, metabolic processes and post-translational modifications are thought to affect the function of RNA protectors...
February 16, 2018: Essays in Biochemistry
https://www.readbyqxmd.com/read/29450416/a-g-quadruplex-motif-at-the-3-end-of-sgrnas-improves-crispr-cas9-based-genome-editing-efficiency
#7
Smita Nahar, Paras Sehgal, Mohd Azhar, Manish Rai, Amrita Singh, Sridhar Sivasubbu, Debojyoti Chakraborty, Souvik Maiti
Originating as a component of prokaryotic adaptive immunity, the type II CRISPR/Cas9 system has been repurposed for targeted genome editing in various organisms. Although Cas9 can bind and cleave DNA efficiently under in vitro conditions, its activity inside a cell can vary dramatically between targets owing to the differences between genomic loci and the availability of enough Cas9/sgRNA (single guide RNA) complex molecules for cleavage. Most methods have so far relied on Cas9 protein engineering or base modifications in the sgRNA sequence to improve CRISPR/Cas9 activity...
February 16, 2018: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/29447396/rna-dna-hybrids-promote-the-expansion-of-friedreich-s-ataxia-gaa-n-repeats-via-break-induced-replication
#8
Alexander J Neil, Miranda U Liang, Alexandra N Khristich, Kartik A Shah, Sergei M Mirkin
Expansion of simple DNA repeats is responsible for numerous hereditary diseases in humans. The role of DNA replication, repair and transcription in the expansion process has been well documented. Here we analyzed, in a yeast experimental system, the role of RNA-DNA hybrids in genetic instability of long (GAA)n repeats, which cause Friedreich's ataxia. Knocking out both yeast RNase H enzymes, which counteract the formation of RNA-DNA hybrids, increased (GAA)n repeat expansion and contraction rates when the repetitive sequence was transcribed...
February 13, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29444946/karyopherin-alpha6-is-required-for-the-replication-of-porcine-reproductive-and-respiratory-syndrome-virus-and-zika-virus
#9
Liping Yang, Rong Wang, Shixing Yang, Zexu Ma, Shaoli Lin, Yuchen Nan, Qisheng Li, Qiyi Tang, Yan-Jin Zhang
Movement of macromolecules between the cytoplasm and the nucleus occurs through the nuclear pore complex (NPC). Karyopherins comprise a family of soluble transport factors facilitating nucleocytoplasmic translocation of proteins through the NPC. In this study, we discovered that karyopherin alpha6 (KPNA6, also known as importin alpha7) was required for the optimal replication of porcine reproductive and respiratory syndrome virus (PRRSV) and Zika virus (ZIKV), which are positive-sense, single-stranded RNA viruses replicating in the cytoplasm...
February 14, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29444942/a-functional-link-between-rna-replication-and-virion-assembly-in-the-potyvirus-plum-pox-virus
#10
Araiz Gallo, Adrian Valli, María Calvo, Juan Antonio García
Accurate assembly of viral particles in the potyvirus Plum pox virus (PPV) has been shown to depend on the contribution of the multifunctional viral protein HCPro. In this study, we show that other viral factors, in addition to the capsid protein (CP) and HCPro, are necessary for the formation of stable PPV virions. The CP produced in Nicotiana benthamiana leaves from a subviral RNA termed LONG, which expresses a truncated polyprotein that lacks P1 and HCPro, together with HCPro supplied in trans , was assembled into virus like particles and remained stable after in vitro incubation...
February 14, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29444437/mutations-in-cytosine-5-trna-methyltransferases-impact-mobile-element-expression-and-genome-stability-at-specific-dna-repeats
#11
Bianca Genenncher, Zeljko Durdevic, Katharina Hanna, Daniela Zinkl, Mehrpouya Balaghy Mobin, Nevcin Senturk, Bruno Da Silva, Carine Legrand, Clément Carré, Frank Lyko, Matthias Schaefer
The maintenance of eukaryotic genome stability is ensured by the interplay of transcriptional as well as post-transcriptional mechanisms that control recombination of repeat regions and the expression and mobility of transposable elements. We report here that mutations in two (cytosine-5) RNA methyltransferases, Dnmt2 and NSun2, impact the accumulation of mobile element-derived sequences and DNA repeat integrity in Drosophila. Loss of Dnmt2 function caused moderate effects under standard conditions, while heat shock exacerbated these effects...
February 13, 2018: Cell Reports
https://www.readbyqxmd.com/read/29444145/waggawagga-cli-a-command-line-tool-for-predicting-stable-single-%C3%AE-helices-sah-domains-and-the-sah-domain-distribution-across-eukaryotes
#12
Dominic Simm, Martin Kollmar
Stable single-alpha helices (SAH-domains) function as rigid connectors and constant force springs between structural domains, and can provide contact surfaces for protein-protein and protein-RNA interactions. SAH-domains mainly consist of charged amino acids and are monomeric and stable in polar solutions, characteristics which distinguish them from coiled-coil domains and intrinsically disordered regions. Although the number of reported SAH-domains is steadily increasing, genome-wide analyses of SAH-domains in eukaryotic genomes are still missing...
2018: PloS One
https://www.readbyqxmd.com/read/29441192/knockdown-of-lncrna-mapt-as1-inhibites-proliferation-and-migration-and-sensitizes-cancer-cells-to-paclitaxel-by-regulating-mapt-expression-in-er-negative-breast-cancers
#13
Yiyuan Pan, Yiqi Pan, Yue Cheng, Fan Yang, Zhihan Yao, Ouchen Wang
Background: MAPT-AS1, a long non-coding RNA, has not been reported in any previous research about its function in cancers. In this study, we investigated the role of MAPT-AS1 in the progression and paclitaxel resistance in breast cancer, and the regulation between MAPT-AS1 and its natural comparable sense transcripts MAPT. Methods: We analysed the breast cancer patients' clinical information and explored the function of MAPT-AS1 by gain- and loss-of function assays in vitro and in vivo...
2018: Cell & Bioscience
https://www.readbyqxmd.com/read/29440403/suppression-of-rgsz1-function-optimizes-the-actions-of-opioid-analgesics-by-mechanisms-that-involve-the-wnt-%C3%AE-catenin-pathway
#14
Sevasti Gaspari, Immanuel Purushothaman, Valeria Cogliani, Farhana Sakloth, Rachael L Neve, David Howland, Robert H Ring, Elliott M Ross, Li Shen, Venetia Zachariou
Regulator of G protein signaling z1 (RGSz1), a member of the RGS family of proteins, is present in several networks expressing mu opioid receptors (MOPRs). By using genetic mouse models for global or brain region-targeted manipulations of RGSz1 expression, we demonstrated that the suppression of RGSz1 function increases the analgesic efficacy of MOPR agonists in male and female mice and delays the development of morphine tolerance while decreasing the sensitivity to rewarding and locomotor activating effects...
February 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29438994/druid-a-pipeline-for-transcriptome-wide-measurements-of-mrna-stability
#15
Andrew Lugowski, Beth Nicholson, Olivia Selfridge Rissland
Control of messenger RNA (mRNA) stability is an important aspect of gene regulation. The gold standard for measuring mRNA stability transcriptome-wide uses metabolic labeling, biochemical isolation of labeled RNA populations, and high-throughput sequencing. However, difficult normalization procedures have inhibited widespread adoption of this approach. Here, we present DRUID (for Determination of Rates Using Intron Dynamics), a new computational pipeline that is robust, easy to use, and freely available. Our pipeline uses endogenous introns to normalize time course data and yields reproducible half-lives, even with datasets that were otherwise unusable...
February 8, 2018: RNA
https://www.readbyqxmd.com/read/29437530/endosomal-escape-of-asos-internalized-by-stabilin-receptors-is-regulated-by-rab5c-and-eea1-during-endosomal-maturation
#16
Colton M Miller, W Brad Wan, Punit P Seth, Edward N Harris
Second-generation (Gen 2) Antisense oligonucleotides (ASOs) show increased nuclease stability and affinity for their RNA targets, which has translated to improved potency and therapeutic index in the clinic. Gen 2 ASOs are typically modified using the phosphorothioate (PS) backbone modification, which enhances ASO interactions with plasma, cell surface, and intracellular proteins. This facilitates ASO distribution to peripheral tissues and also promotes cellular uptake after injection into animals. Previous work identified that Stabilin receptors specifically internalize PS-ASOs in the sinusoidal endothelial cells of the liver and the spleen...
February 13, 2018: Nucleic Acid Therapeutics
https://www.readbyqxmd.com/read/29436491/long-non-coding-rna-linc00657-acting-as-mir-590-3p-sponge-to-facilitate-low-concentration-oxidized-low-density-lipoprotein-induced-angiogenesis
#17
Mei-Hua Bao, Guang-Yi Li, Xiao-Shan Huang, Liang Tang, Li-Ping Dong, Jian-Ming Li
Angiogenesis in atherosclerotic plaque promotes plaque growth, causes plaque hemorrhage and violates plaque stability. LINC00657 is a long noncoding RNA highly conserved and abundantly expressed in vascular endothelial cells. The present study was designed to investigate the effects and mechanisms of LINC00675 on the low concentration of oxidized low-density lipoprotein (oxLDL) induced angiogenesis. Cell proliferation assay, transwell assay, wound healing assay, and tube formation assay were conducted to detect the effects of low concentration of oxLDL on angiogenesis; The results discovered that oxLDL promoted the cell proliferation, migration, and tube formation...
February 7, 2018: Molecular Pharmacology
https://www.readbyqxmd.com/read/29435408/a-putative-rna-binding-protein-from-plasmodium-vivax-apicoplast
#18
Sofía M García-Mauriño, Antonio Díaz-Quintana, Francisco Rivero-Rodríguez, Isabel Cruz-Gallardo, Christian Grüttner, Marian Hernández-Vellisca, Irene Díaz-Moreno
Malaria is caused by Apicomplexa protozoans from the Plasmodium genus entering the bloodstream of humans and animals through the bite of the female mosquitoes. The annotation of the Plasmodium vivax genome revealed a putative RNA binding protein (apiRBP) that was predicted to be trafficked into the apicoplast, a plastid organelle unique to Apicomplexa protozoans. Although a 3D structural model of the apiRBP corresponds to a noncanonical RNA recognition motif with an additional C-terminal α-helix (α3), preliminary protein production trials were nevertheless unsuccessful...
February 2018: FEBS Open Bio
https://www.readbyqxmd.com/read/29434035/molecular-dynamics-correctly-models-the-unusual-major-conformation-of-the-gagu-rna-internal-loop-and-with-nmr-reveals-an-unusual-minor-conformation
#19
Aleksandar Spasic, Scott D Kennedy, Laura Needham, Muthiah Manoharan, Ryszard Kierzek, Douglas H Turner, David Mathews
The RNA "GAGU" duplex, (5'GACGAGUGUCA)2, contains the internal loop (5'-GAGU-3')2 , which has two conformations in solution as determined by NMR spectroscopy. The major conformation has a loop structure consisting of trans-Watson-Crick/Hoogsteen GG pairs, two A residues stacked on each other, two U residues bulged outside the helix and exposed to solvent, and all sugars with a C2'-endo conformation. This differs markedly from the internal loops, (5'-GAGC-3')2 , (5'-AAGU-3')2 and (5'-UAGG-3')2, which all have cis-Watson-Crick/Watson-Crick AG "imino" non-canonical pairs flanked by cis Watson-Crick/Watson-Crick canonical pairs resulting in maximal hydrogen bonding...
February 6, 2018: RNA
https://www.readbyqxmd.com/read/29433542/smurf1-facilitates-estrogen-receptor-%C3%A9-signaling-in-breast-cancer-cells
#20
Huijie Yang, Na Yu, Juntao Xu, Xiaosheng Ding, Wei Deng, Guojin Wu, Xin Li, Yingxiang Hou, Zhenhua Liu, Yan Zhao, Min Xue, Sifan Yu, Beibei Wang, Xiumin Li, Gang Niu, Hui Wang, Jian Zhu, Ting Zhuang
BACKGROUND: Estrogen receptor alpha (ER alpha) is expressed in the majority of breast cancers and promotes estrogen-dependent cancer progression. ER alpha positive breast cancer can be well controlled by ER alpha modulators, such as tamoxifen. However, tamoxifen resistance is commonly observed by altered ER alpha signaling. Thus, further understanding of the molecular mechanisms, which regulates ER alpha signaling, is important to improve breast cancer therapy. METHODS: SMURF1 and ER alpha protein expression levels were measured by western blot, while the ER alpha target genes were measured by real-time PCR...
February 12, 2018: Journal of Experimental & Clinical Cancer Research: CR
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