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https://www.readbyqxmd.com/read/28431250/nuclear-proximity-of-mtr4-to-rna-exosome-restricts-dna-mutational-asymmetry
#1
Junghyun Lim, Pankaj Kumar Giri, David Kazadi, Brice Laffleur, Wanwei Zhang, Veronika Grinstein, Evangelos Pefanis, Lewis M Brown, Erik Ladewig, Ophélie Martin, Yuling Chen, Raul Rabadan, François Boyer, Gerson Rothschild, Michel Cogné, Eric Pinaud, Haiteng Deng, Uttiya Basu
The distribution of sense and antisense strand DNA mutations on transcribed duplex DNA contributes to the development of immune and neural systems along with the progression of cancer. Because developmentally matured B cells undergo biologically programmed strand-specific DNA mutagenesis at focal DNA/RNA hybrid structures, they make a convenient system to investigate strand-specific mutagenesis mechanisms. We demonstrate that the sense and antisense strand DNA mutagenesis at the immunoglobulin heavy chain locus and some other regions of the B cell genome depends upon localized RNA processing protein complex formation in the nucleus...
April 20, 2017: Cell
https://www.readbyqxmd.com/read/28430659/lncrna-afap1-as1-promotes-growth-and-metastasis-of-cholangiocarcinoma-cells
#2
Xiuhui Shi, Hang Zhang, Min Wang, Xiaodong Xu, Yan Zhao, Ruizhi He, Min Zhang, Min Zhou, Xu Li, Feng Peng, Chengjian Shi, Ming Shen, Xin Wang, Xingjun Guo, Renyi Qin
We investigated the role of actin filament associated protein 1 antisense RNA1 (AFAP1-AS1) lncRNA in promoting cholangiocarcinoma (CCA). qRT-PCR analysis of patient samples showed that AFAP1-AS1 expression was higher in CCA tumors than matched adjacent non-tumor tissue. AFAP1-AS1 levels were also higher in CCA cell lines (HuCCT1 and TFK-1) than a normal biliary epithelium cell line (HIBEpic). AFAP1-AS1 knockdown in CCA cell lines using shAFAP1-AS1 reduced cell proliferation and colony formation in CCK-8 and colony formation assays, respectively...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427205/mns16a-tandem-repeat-minisatellite-of-human-telomerase-gene-functional-studies-in-colorectal-lung-and-prostate-cancer
#3
Philipp Hofer, Cornelia Zöchmeister, Christian Behm, Stefanie Brezina, Andreas Baierl, Angelina Doriguzzi, Vanita Vanas, Klaus Holzmann, Hedwig Sutterlüty-Fall, Andrea Gsur
MNS16A, a functional polymorphic tandem repeat minisatellite, is located in the promoter region of an antisense transcript of the human telomerase reverse transcriptase gene. MNS16A promoter activity depends on the variable number of tandem repeats (VNTR) presenting varying numbers of transcription factor binding sites for GATA binding protein 1. Although MNS16A has been investigated in multiple cancer epidemiology studies with incongruent findings, functional data of only two VNTRs (VNTR-243 and VNTR-302) were available thus far, linking the shorter VNTR to higher promoter activity...
March 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28426097/landscape-of-rna-polyadenylation-in-e-coli
#4
Alexandre Maes, Céline Gracia, Nicolas Innocenti, Kaiyang Zhang, Erik Aurell, Eliane Hajnsdorf
Polyadenylation is thought to be involved in the degradation and quality control of bacterial RNAs but relatively few examples have been investigated. We used a combination of 5΄-tagRACE and RNA-seq to analyze the total RNA content from a wild-type strain and from a poly(A)polymerase deleted mutant. A total of 178 transcripts were either up- or down-regulated in the mutant when compared to the wild-type strain. Poly(A)polymerase up-regulates the expression of all genes related to the FliA regulon and several previously unknown transcripts, including numerous transporters...
March 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28426096/managing-the-sequence-specificity-of-antisense-oligonucleotides-in-drug-discovery
#5
Peter H Hagedorn, Bo R Hansen, Troels Koch, Morten Lindow
All drugs perturb the expression of many genes in the cells that are exposed to them. These gene expression changes can be divided into effects resulting from engaging the intended target and effects resulting from engaging unintended targets. For antisense oligonucleotides, developments in bioinformatics algorithms, and the quality of sequence databases, allow oligonucleotide sequences to be analyzed computationally, in terms of the predictability of their interactions with intended and unintended RNA targets...
March 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28423565/identification-and-characterization-of-l1-specific-endo-sirnas-essential-for-early-embryonic-development-in-pig
#6
Heng Zhang, Jilong Liu, Yurong Tai, Xiaolei Zhang, Jiaming Zhang, Shichao Liu, Jiawei Lv, Zhonghua Liu, Qingran Kong
Small noncoding RNAs (sncRNAs) play important roles in RNA interference (RNAi). In addition to microRNA (miRNA) and Piwi-interacting RNA (piRNA), one key member of sncRNAs group is endogenous small interfering RNA (endo-siRNA). Some studies do show the role of endo-siRNAs in Dicer and/or Ago mutants, however, the biological functions of specific endo-siRNAs remains mostly unanswered. In the study, we have performed a comparative analysis of endo-siRNAs present in porcine sperms, oocytes and zygotes, identified by deep sequencing and bioinformatics analysis...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421099/progress-in-high-amylose-cereal-crops-through-inactivation-of-starch-branching-enzymes
#7
REVIEW
Juan Wang, Pan Hu, Zichun Chen, Qiaoquan Liu, Cunxu Wei
High-amylose cereal starches provide many health benefits for humans. The inhibition or mutation of starch branching enzyme (SBE) genes is an effective method to develop high-amylose cereal crops. This review summarizes the development of high-amylose cereal crops through the inactivation of one or more SBE isoforms or combination with other genes. This review also reveals the causes of increase in amylose content in high-amylose crops. A series of changes, including amylopectin structure, crystalline structure, thermal properties, and hydrolysis properties, occurs as amylose content increases...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28420874/therapeutic-targeting-using-tumor-specific-peptides-inhibits-long-non-coding-rna-hotair-activity-in-ovarian-and-breast-cancer
#8
Ali R Özeş, Yinu Wang, Xingyue Zong, Fang Fang, Jay Pilrose, Kenneth P Nephew
Long non-coding RNAs (lncRNAs) play key roles in human diseases, including cancer. Functional studies of the lncRNA HOTAIR (HOX transcript antisense RNA) provide compelling evidence for therapeutic targeting of HOTAIR in cancer, but targeting lncRNAs in vivo has proven to be difficult. In the current study, we describe a peptide nucleic acids (PNA)-based approach to block the ability of HOTAIR to interact with EZH2 and subsequently inhibit HOTAIR-EZH2 activity and resensitize resistant ovarian tumors to platinum...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28420437/bidirectional-nucleolar-dysfunction-in-c9orf72-frontotemporal-lobar-degeneration
#9
Sarah Mizielinska, Charlotte E Ridler, Rubika Balendra, Annora Thoeng, Nathan S Woodling, Friedrich A Grässer, Vincent Plagnol, Tammaryn Lashley, Linda Partridge, Adrian M Isaacs
An intronic GGGGCC expansion in C9orf72 is the most common known cause of both frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). The repeat expansion leads to the generation of sense and antisense repeat RNA aggregates and dipeptide repeat (DPR) proteins, generated by repeat-associated non-ATG translation. The arginine-rich DPR proteins poly(glycine-arginine or GR) and poly(proline-arginine or PR) are potently neurotoxic and can localise to the nucleolus when expressed in cells, resulting in enlarged nucleoli with disrupted functionality...
April 18, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28418770/gene-silencing-activity-and-hepatic-accumulation-of-antisense-oligonucleotides-bearing-cholesterol-conjugated-thiono-triester-at-the-gap-region
#10
Mado Nakajima, Takeshi Kasuya, Shinnichi Yokota, Reina Onishi, Tatsuya Ikehara, Akira Kugimiya, Ayahisa Watanabe
Cholesterol (Chol) conjugation to the 5' or 3' end of antisense oligonucleotide (ASO) enables delivery to the liver, and Chol conjugation at the gap region can also be expected to improve delivery to the liver. In this study, we synthesized ASOs bearing the Chol-conjugated thiono triester and evaluated their activity and hepatic accumulation. We found that Chol conjugations at the gap region improved in vitro activity and hepatic accumulation when compared to unconjugated ASOs. However, Chol conjugation with phosphorothioate linkage did not improve in vivo activity in the liver, suggesting the importance of cleaving the phosphodiester between ASO and Chol...
April 18, 2017: Nucleic Acid Therapeutics
https://www.readbyqxmd.com/read/28418733/feasibility-of-spect-ct-imaging-to-study-the-pharmacokinetics-of-antisense-oligonucleotides-in-a-mouse-model-of-duchenne-muscular-dystrophy
#11
Evita van de Steeg, Tilman Läppchen, Begoña Aguilera, Harm T Jansen, Daan Muilwijk, Rick Vermue, José W van der Hoorn, Katia Donato, Raffaella Rossin, Peter C de Visser, Maria L H Vlaming
Antisense oligonucleotides (AONs) are promising candidates for treatment of Duchenne muscular dystrophy (DMD), a severe and progressive disease resulting in premature death. However, more knowledge on the pharmacokinetics of new AON drug candidates is desired for effective application in the clinic. We assessed the feasibility of using noninvasive single-photon emission computed tomography-computed tomography (SPECT-CT) imaging to determine AON pharmacokinetics in vivo. To this end, a 2'-O-methyl phosphorothioate AON was radiolabeled with (123)I or (111)In, and administered to mdx mice, a rodent model of DMD...
April 18, 2017: Nucleic Acid Therapeutics
https://www.readbyqxmd.com/read/28415631/lncrna-hotair-acts-a-competing-endogenous-rna-to-control-the-expression-of-notch3-via-sponging-mir-613-in-pancreatic-cancer
#12
Huihua Cai, Jie Yao, Yong An, Xuemin Chen, Weibo Chen, Di Wu, Boyang Luo, Yong Yang, Yong Jiang, Donglin Sun, Xiaozhou He
Pancreatic cancer is one of the most deadly cancers with a poor prognosis. Though studies have implicated the roles of microRNAs in pancreatic cancer progression, little is known about the role of miR-613 in pancreatic cancer. In the present study, the expression of miR-613 was down-regulated in pancreatic cancer tissues and cancer cell lines. Down-regulation of miR-613 was positively correlated with tumor differentiation, advanced TNM stage, nodal metastasis and shorter overall survival in patients with pancreatic cancer...
March 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415063/neuron-restrictive-silencer-factor-mediated-downregulation-of-%C3%AE-opioid-receptor-contributes-to-the-reduced-morphine-analgesia-in-bone-cancer-pain
#13
Chao Zhu, Jun Tang, Tan Ding, Lei Chen, Wei Wang, Xiao-Peng Mei, Xiao-Tao He, Wen Wang, Li-Dong Zhang, Yu-Lin Dong, Zhuo-Jing Luo
Bone cancer pain has been reported to have unique mechanisms and is resistant to morphine treatment. Recent studies have indicated that neuron-restrictive silencer factor (NRSF) plays a crucial role in modulating the expression of the μ-opioid receptor (MOR) gene. The present study elucidates the regulatory mechanisms of MOR and its ability to affect bone cancer pain. Using a sarcoma-inoculated murine model, pain behaviors that represent continuous or breakthrough pain were evaluated. Expression of NRSF in the dorsal root ganglion (DRG) and spinal dorsal horn was quantified at the transcriptional and translational levels, respectively...
May 2017: Pain
https://www.readbyqxmd.com/read/28412515/genome-wide-determination-of-transcription-start-sites-reveals-new-insights-into-promoter-structures-in-the-actinomycete-corynebacterium-glutamicum
#14
Andreas Albersmeier, Katharina Pfeifer-Sancar, Christian Rückert, Jörn Kalinowski
The genome-wide identification of transcription start sites, enabled by high-throughput sequencing of a cDNA library enriched for native 5' transcript ends, is ideally suited for the analysis of promoters. Here, the transcriptome of Corynebacterium glutamicum, a non-pathogenic soil bacterium from the actinomycetes branch that is used in industry for the production of amino acids, was analysed by transcriptome sequencing of the 5'-ends of native transcripts. Total RNA samples were harvested from the exponential phase of growth, therefore the study mainly addressed promoters recognized by the main house-keeping sigma factor σ(A)...
April 12, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28412171/gender-specific-amelioration-of-sma-phenotype-upon-disruption-of-a-deep-intronic-structure-by-an-oligonucleotide
#15
Matthew D Howell, Eric W Ottesen, Natalia N Singh, Rachel L Anderson, Ravindra N Singh
Spinal muscular atrophy (SMA), the leading genetic disease of children, is caused by low levels of survival motor neuron (SMN) protein. Here, we employ A15/283, an antisense oligonucleotide targeting a deep intronic sequence/structure, to examine the impact of restoration of SMN in a mild SMA mouse model. We show gender-specific amelioration of tail necrosis upon subcutaneous administrations of A15/283 into SMA mice at postnatal days 1 and 3. We also demonstrate that a modest increase in SMN due to early administrations of A15/283 dramatically improves testicular development and spermatogenesis...
April 13, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28411216/construction-of-a-dcas9-based-gene-knockdown-system-in-staphylococcus-aureus
#16
Changlong Zhao, Xueqin Shu, Baolin Sun
There has been constant absence of an efficient gene knockdown method in the important human pathogen Staphylococcus aureus like RNA interference in eukaryotes. The early developed antisense RNA technology is mainly applied for forward genetic screen, but is rather limiting in specific gene knockdown for the lack of rational antisense RNA design strategies. Here we report an efficient and specific gene knockdown system in S. aureus based on type II clustered regularly interspaced short palindromic repeats (CRISPR) system from Streptococcus pyogenes...
April 14, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28410229/in-vivo-evaluation-of-the-effects-of-simultaneous-inhibition-of-glut-1-and-hif-1%C3%AE-by-antisense-oligodeoxynucleotides-on-the-radiosensitivity-of-laryngeal-carcinoma-using-micro-18f-fdg-pet-ct
#17
Li-Fang Shen, Xin Zhao, Shui-Hong Zhou, Zhong-Jie Lu, Kui Zhao, Jun Fan, Min-Li Zhou
PURPOSE: Hypoxia-inducible factor 1α (HIF-1α) and glucose transporter-1 (GLUT-1) are two important hypoxic markers associated with the radioresistance of cancers including laryngeal carcinoma. We evaluated whether the simultaneous inhibition of GLUT-1 and HIF-1α expression improved the radiosensitivity of laryngeal carcinoma. We explored whether the expression of HIF-1α and GLUT-1 was correlated with 2'-deoxy-2'-[18F]fluoro-D-glucose (18F-FDG) uptake and whether 18F-FDG positron emission tomography-computed tomography (PET/CT) was appropriate for early evaluation of the response of laryngeal carcinoma to targeted treatment in vivo...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28410209/mir-106b-inhibitors-sensitize-trail-induced-apoptosis-in-hepatocellular-carcinoma-through-increase-of-death-receptor-4
#18
Changlong Xu, Liang Shi, Weilai Chen, Peipei Fang, Jie Li, Lingxiang Jin, Zhenzhen Pan, Chenwei Pan
TNF-related apoptosis-inducing ligand (TRAIL), which is a member of the TNF superfamily, can induce tumor cell apoptosis. However, multiple types of tumor, including hepatocellular carcinoma, show tolerance to TRAIL. Previous studies have demonstrated that tumor cells usually change their expression profile of microRNA (miRNA) to obtain the ability of tolerance to drugs. However, whether such change of miRNA on TRAIL sensitivity is seen in hepatocellular carcinoma still needs to be explored. In this study, we observed overexpression of miR-106b in both HCC patients' tumor tissues and cell lines...
March 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28409342/zebrafish-as-a-model-of-kidney-disease
#19
Elvin E Morales, Rebecca A Wingert
Animal models have been an invaluable means to advance biomedical research as they provide experimental avenues for cellular and molecular investigations of disease pathology. The zebrafish (Danio rerio) is a good alternative to mammalian models that can be used to apply powerful genetic experimental methods normally used in invertebrates to answer questions about vertebrate development and disease. In the case of the kidney, the zebrafish has proven itself to be an applicable and versatile experimental system, mainly due to the simplicity of its pronephros, which contains two nephrons that possess conserved structural and physiological aspects with mammalian nephrons...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/28408313/preventing-cardiovascular-heart-disease-promising-nutraceutical-and-non-nutraceutical-treatments-for-cholesterol-management
#20
REVIEW
T P Johnston, T A Korolenko, M Pirro, A Sahebkar
Hypercholesterolemia is one of the major risk factors for the development of cardiovascular disease. Atherosclerosis resulting from hypercholesterolemia causes many serious cardiovascular diseases. Statins are generally accepted as a treatment of choice for lowering low-density lipoprotein (LDL) cholesterol, which reduces coronary heart disease morbidity and mortality. Since statin use can be associated with muscle problems and other adverse symptoms, non-adherence and discontinuation of statin therapy often leads to inadequate control of plasma cholesterol levels and increased cardiovascular risk...
April 10, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
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