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https://www.readbyqxmd.com/read/28817209/huntington-s-disease-a-clinical-review
#1
Peter McColgan, Sarah J Tabrizi
Huntington's disease (HD) is a fully penetrant neurodegenerative disease caused by a dominantly inherited CAG trinucleotide repeat expansion in the huntingtin gene on chromosome 4. In Western populations HD has a prevalence of 10.6-13.7 individuals per 100,000. It is characterised by cognitive, motor and psychiatric disturbance. At the cellular level mutant huntingtin results in neuronal dysfunction and death through a number of mechanisms, including disruption of proteostasis, transcription and mitochondrial function and direct toxicity of the mutant protein...
August 17, 2017: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/28815537/from-heterochromatin-to-long-noncoding-rnas-in-drosophila-expanding-the-arena-of-gene-function-and-regulation
#2
Subhash C Lakhotia
Recent years have witnessed a remarkable interest in exploring the significance of pervasive noncoding transcripts in diverse eukaryotes. Classical cytogenetic studies using the Drosophila model system unraveled the perplexing attributes and "functions" of the "gene"-poor heterochromatin. Recent molecular studies in the fly model are likewise revealing the very diverse and significant roles played by long noncoding RNAs (lncRNAs) in development, gene regulation, chromatin organization, cell and nuclear architecture, etc...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28811264/protein-coding-genes-as-hosts-for-noncoding-rna-expression
#3
REVIEW
Vincent Boivin, Gabrielle Deschamps-Francoeur, Michelle S Scott
With the emergence of high-throughput sequence characterization methods and the subsequent improvements in gene annotations, it is becoming increasingly clear that a large proportion of eukaryotic protein-coding genes (as many as 50% in human) serve as host genes for non-coding RNA genes. Amongst the most extensively characterized embedded non-coding RNA genes, small nucleolar RNAs and microRNAs represent abundant families. Encoded individually or clustered, in sense or antisense orientation with respect to their host and independently expressed or dependent on host expression, the genomic characteristics of embedded genes determine their biogenesis and the extent of their relationship with their host gene...
August 12, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28807725/the-rnf146-e3-ubiquitin-ligase-is-required-for-the-control-of-wnt-signaling-and-body-pattern-formation-in-xenopus
#4
Xuechen Zhu, Rui Xing, Renbo Tan, Rongyang Dai, Qinghua Tao
The RING finger protein Rnf146 encodes an E3 ubiquitin ligase capable of targeting poly-ADP-ribosylated substrates for proteasomal degradation. Rnf146 has been identified as a critical regulator of Axin1 and thus of Wnt/β-catenin signaling. However its physiological significance in vertebrate embryonic development remains to be demonstrated. In this study, we take advantages of early Xenopus embryos to demonstrate that Rnf146 is essential for embryonic pattern formation. Depletion of zygotic Rnf146 using a translation blocking morpholino oligo (MO) results in anteriorized development and increased expression the anterior marker gene Otx2, consistent the notion that Rnf146 is a positive regulator of Wnt/β-catenin signaling through negatively regulating Axin1 expression...
August 11, 2017: Mechanisms of Development
https://www.readbyqxmd.com/read/28806224/bromodomain-containing-protein-4-activates-voltage-gated-sodium-channel-1-7-transcription-in-dorsal-root-ganglia-neurons-to-mediate-thermal-hyperalgesia-in-rats
#5
Ming-Chun Hsieh, Yu-Cheng Ho, Cheng-Yuan Lai, Hsueh-Hsiao Wang, An-Sheng Lee, Jen-Kun Cheng, Yat-Pang Chau, Hsien-Yu Peng
BACKGROUND: Bromodomain-containing protein 4 binds acetylated promoter histones and promotes transcription; however, the role of bromodomain-containing protein 4 in inflammatory hyperalgesia remains unclear. METHODS: Male Sprague-Dawley rats received hind paw injections of complete Freund's adjuvant to induce hyperalgesia. The dorsal root ganglia were examined to detect changes in bromodomain-containing protein 4 expression and the activation of genes involved in the expression of voltage-gated sodium channel 1...
August 11, 2017: Anesthesiology
https://www.readbyqxmd.com/read/28803245/mir-143-5p-deficiency-triggers-emt-and-metastasis-by-targeting-hif-1%C3%AE-in-gallbladder-cancer
#6
Min He, Ming Zhan, Wei Chen, Sunwang Xu, Manmei Long, Hui Shen, Yongheng Shi, Qiang Liu, Man Mohan, Jian Wang
BACKGROUND/AIMS: Early metastasis plays a pivotal role in tumor-caused death in gallbladder cancer (GBC) patients. Increasing evidence suggest that miR-143-5p is an active player involved in cancer metastasis and a potential therapeutic target. However, its role in the development of GBC cells remains unclear. The aim of this study is to reveal the inhibiting effects of miR-143-5p on the proliferation and metastasis in GBC. METHODS: Quantitative real-time PCR were used to investigate miR-143-5p and its target HIF-1α mRNA levels...
August 11, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28799578/nusinersen-antisense-oligonucleotide-to-increase-smn-protein-production-in-spinal-muscular-atrophy
#7
D M Paton
Patients with spinal muscular atrophy (SMA) have an autosomal recessive disease that limits their ability to produce survival motor neuron (SMN) protein in the CNS resulting in progressive wasting of voluntary muscles. Detailed studies over several years have demonstrated that phosphorothioate and 2'-O-methoxyethyl- modified antisense oligonucleotides (ASOs) targeting the ISS-N1 site increase SMN2 exon 7 inclusion, thus increasing levels of SMN protein in a dose- and time-dependent manner in liver, kidney and skeletal muscle, and CNS tissues only when administered intrathecally...
June 2017: Drugs of Today
https://www.readbyqxmd.com/read/28796573/development-of-exon-skipping-therapies-for-duchenne-muscular-dystrophy-a-critical-review-and-a-perspective-on-the-outstanding-issues
#8
Annemieke Aartsma-Rus, Volker Straub, Robert Hemmings, Manuel Haas, Gabriele Schlosser-Weber, Violeta Stoyanova-Beninska, Eugenio Mercuri, Francesco Muntoni, Bruno Sepodes, Elizabeth Vroom, Pavel Balabanov
Duchenne muscular dystrophy (DMD) is a rare, severe, progressive muscle-wasting disease leading to disability and premature death. Patients lack the muscle membrane-stabilizing protein dystrophin. Antisense oligonucleotide (AON)-mediated exon skipping is a therapeutic approach that aims to induce production of partially functional dystrophins. Recently, an AON targeting exon 51 became the first of its class to be approved by the United States regulators [Food and Drug Administration (FDA)] for the treatment of DMD...
August 10, 2017: Nucleic Acid Therapeutics
https://www.readbyqxmd.com/read/28794451/vitamin-b12-as-a-carrier-of-peptide-nucleic-acid-pna-into-bacterial-cells
#9
Marcin Równicki, Monika Wojciechowska, Aleksandra J Wierzba, Jakub Czarnecki, Dariusz Bartosik, Dorota Gryko, Joanna Trylska
Short modified oligonucleotides targeted at bacterial DNA or RNA could serve as antibacterial agents provided that they are efficiently taken up by bacterial cells. However, the uptake of such oligonucleotides is hindered by the bacterial cell wall. To overcome this problem, oligomers have been attached to cell-penetrating peptides, but the efficiency of delivery remains poor. Thus, we have investigated the ability of vitamin B12 to transport peptide nucleic acid (PNA) oligomers into cells of Escherichia coli and Salmonella Typhimurium...
August 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28791413/knockdown-of-hotair-suppresses-proliferation-and-cell-cycle-progression-in-hepatocellular-carcinoma-cell-by-downregulating-ccnd1-expression
#10
Jia-Jia Zhou, Di Cheng, Xiao-Yu He, Zhe Meng, Wen-Zhu Li, Ru-Fu Chen
The long noncoding RNA, homeobox transcript antisense RNA (Hotair), has been demonstrated to have an important role in regulating various biological processes in various cancers, including hepatocellular carcinoma (HCC). However, the importance of Hotair in HCC proliferation and cell cycle progression remains to be elucidated. In the present study, knockdown of HOTAIR expression by RNA interference inhibited cell proliferation and induced G0/G1 cell cycle arrest in Huh7 hepatocellular carcinoma cells. In addition, the expression levels of CCND1 mRNA and its cyclin D1 protein product were reduced in Huh7 cells following knockdown of HOTAIR...
August 3, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28790838/downregulation-of-lncrna-sdpr-as-is-associated-with-poor-prognosis-in-renal-cell-carcinoma
#11
Wenjun Ni, Erlin Song, Mancheng Gong, Yongxiang Li, Jie Yao, Ruihua An
Renal cell carcinoma (RCC) is a common type of kidney cancer. Normally, surgical treatment can prolong life, but only for patients with early stage tumors. However, it is difficult for early detection strategies to distinguish between benign and malignant kidney tumors. Therefore, potential biomarkers for early diagnosis and prognosis of RCC are needed. Intriguingly, mounting evidence has demonstrated that many long noncoding RNAs (lncRNAs) are strongly linked to cancers. Indeed, promising RCC-associated lncRNA biomarkers have also been identified...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28790409/plant-organ-evolution-revealed-by-phylotranscriptomics-in-arabidopsis-thaliana
#12
Li Lei, Joshua G Steffen, Edward J Osborne, Christopher Toomajian
The evolution of phenotypes occurs through changes both in protein sequence and gene expression levels. Though much of plant morphological evolution can be explained by changes in gene expression, examining its evolution has challenges. To gain a new perspective on organ evolution in plants, we applied a phylotranscriptomics approach. We combined a phylostratigraphic approach with gene expression based on the strand-specific RNA-seq data from seedling, floral bud, and root of 19 Arabidopsis thaliana accessions to examine the age and sequence divergence of transcriptomes from these organs and how they adapted over time...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28782472/canonical-microrna-matching-differs-greatly-across-groups-of-g-protein-coupled-receptor-mrnas
#13
Michael S Parker, Ambikaipakan Balasubramaniam, Floyd R Sallee, Steven L Parker
BACKGROUND: Heptahelical G protein coupled receptors (GPCRs) support numerous sensory and metabolic functions and differ considerably in levels of expression. GPCR protein levels should link to regulation of GPCR mRNAs by microRNAs (miRs), which might significantly depend on numbers, size and GC content of the canonical antisense matches in mRNAs. These parameters of GPCR mRNAs have not been studied in detail. METHODS: Canonical matching profiles of human GPCR mRNAs and miRs were examined using segments of 7-15 nucleotides in windows shifted by one position over the entire microRNA sequence...
August 4, 2017: MicroRNA
https://www.readbyqxmd.com/read/28782268/reprogramming-antagonizes-the-oncogenicity-of-hoxa13-long-noncoding-rna-hottip-axis-in-gastric-cancer-cells
#14
Deng-Chyang Wu, Sophie S W Wang, Chung-Jung Liu, Kenly Wuputra, Kohsuke Kato, Yen-Liang Lee, Ying-Chu Lin, Ming-Ho Tsai, Chia-Chen Ku, Wen-Hsin Lin, Shin-Wei Wang, Shotaro Kishikawa, Michiya Noguchi, Chu-Chieh Wu, Yi-Ting Chen, Chee-Yin Chai, Chen-Lung Steve Lin, Kung-Kai Kuo, Ya-Han Yang, Hiroyuki Miyoshi, Yukio Nakamura, Shigeo Saito, Kyosuke Nagata, Chang-Shen Lin, Kazunari K Yokoyama
Reprogramming of cancer cells into induced pluripotent stem (iPSCs) is a compelling idea for inhibiting oncogenesis, especially through modulation of homeobox proteins in this reprogramming process. We examined the role of various long noncoding RNAs (lncRNAs)-homeobox protein HOXA13 axis on the switching of the oncogenic function of bone morphogenetic protein 7 (BMP7), which is significantly lost in the gastric cancer cell derived iPS-like cells (iPSLCs). BMP promoter activation occurred through the corecruitment of HOXA13, mixed-lineage leukemia 1 lysine N-methyltransferase (MLL1), WD repeat-containing protein 5 (WDR5), and lncRNA HoxA transcript at the distal tip (HOTTIP) to commit the epigenetic changes to the trimethylation of lysine 4 on histone H3 in cancer cells...
August 7, 2017: Stem Cells
https://www.readbyqxmd.com/read/28768861/positive-and-negative-regulation-of-type-i-interferons-by-the-human-t-cell-leukemia-virus-antisense-protein-hbz
#15
Manraj Singh Narulla, Ahlam Alsairi, Lucie Charmier, Stephen Noonan, David Conroy, William W Hall, Noreen Sheehy
The pathogenesis of human T-cell leukemia virus type 1 (HTLV-1) is strongly linked to the viral regulatory proteins Tax1 and HBZ, whose opposing functions contribute to the clinical outcome of infection. Type I interferons α and β (IFNα and IFNβ) are key cytokines involved in innate immunity and IFNα, in combination with other antivirals, is extensively used in the treatment of HTLV-1 infection. The relationship between HTLV-1 and IFN signaling is unclear and to date the effect of HBZ on this pathway has not been examined...
August 2, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28768735/therapeutic-strategies-for-spinal-muscular-atrophy-smn-and-beyond
#16
REVIEW
Melissa Bowerman, Catherina G Becker, Rafael J Yáñez-Muñoz, Ke Ning, Matthew J A Wood, Thomas H Gillingwater, Kevin Talbot
Spinal muscular atrophy (SMA) is a devastating neuromuscular disorder characterized by loss of motor neurons and muscle atrophy, generally presenting in childhood. SMA is caused by low levels of the survival motor neuron protein (SMN) due to inactivating mutations in the encoding gene SMN1 A second duplicated gene, SMN2, produces very little but sufficient functional protein for survival. Therapeutic strategies to increase SMN are in clinical trials, and the first SMN2-directed antisense oligonucleotide (ASO) therapy has recently been licensed...
August 1, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28762207/the-efficacy-of-antisense-based-construct-for-inducing-resistance-against-croton-yellow-vein-mosaic-virus-in-nicotiana-tabacum
#17
V Sinha, N B Sarin, D Bhatnagar
Begomoviruses have increased pathogenicity because of their adaptation to a wide host range; consequently, these viruses cause a major loss to agroeconomic crops worldwide. In this study, we designed a gene construct representing an antisense coat protein gene. We also analyzed the efficacy of the induced resistance against Croton yellow vein mosaic virus (CrYVMV) affecting papaya in Nicotiana tabacum plants. Positive control plants developed typical leaf curl symptoms, whereas transgenic plants were symptomless...
July 31, 2017: Virus Genes
https://www.readbyqxmd.com/read/28761819/legionella-pneumophila-and-dendrimers-mediated-antisense-therapy
#18
REVIEW
Roghiyeh Pashaei-Asl, Khodadad Khodadadi, Fatima Pashaei-Asl, Gholamreza Haqshenas, Nasser Ahmadian, Maryam Pashaiasl, Reza Hajihosseini Baghdadabadi
Finding novel and effective antibiotics for treatment of Legionella disease is a challenging field. Treatment with antibiotics usually cures Legionella infection; however, if the resultant disease is not timely recognized and treated properly, it leads to poor prognosis and high case fatality rate. Legionella pneumophila DrrA protein (Defects in Rab1 recruitment protein A)/also known as SidM affects host cell vesicular trafficking through modification of the activity of cellular small guanosine triphosphatase )GTPase( Rab (Ras-related in brain) function which facilitates intracellular bacterial replication within a supporter vacuole...
June 2017: Advanced Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28759043/genome-wide-screen-for-differentially-methylated-long-noncoding-rnas-identifies-esrp2-and-lncrna-esrp2-as-regulated-by-enhancer-dna-methylation-with-prognostic-relevance-for-human-breast-cancer
#19
K Heilmann, R Toth, C Bossmann, K Klimo, C Plass, C Gerhauser
The majority of long noncoding RNAs (lncRNAs) is still poorly characterized with respect to function, interactions with protein-coding genes, and mechanisms that regulate their expression. As for protein-coding RNAs, epigenetic deregulation of lncRNA expression by alterations in DNA methylation might contribute to carcinogenesis. To provide genome-wide information on lncRNAs aberrantly methylated in breast cancer we profiled tumors of the C3(1) SV40TAg mouse model by MCIp-seq (Methylated CpG Immunoprecipitation followed by sequencing)...
July 31, 2017: Oncogene
https://www.readbyqxmd.com/read/28758689/the-antiphasic-regulatory-module-comprising-cdf5-and-its-antisense-rna-flore-links-the-circadian-clock-to-photoperiodic-flowering
#20
Rossana Henriques, Huan Wang, Jun Liu, Marc Boix, Li-Fang Huang, Nam-Hai Chua
Circadian rhythms of gene expression are generated by the combinatorial action of transcriptional and translational feedback loops as well as chromatin remodelling events. Recently, long noncoding RNAs (lncRNAs) that are natural antisense transcripts (NATs) to transcripts encoding central oscillator components were proposed as modulators of core clock function in mammals (Per) and fungi (frq/qrf). Although oscillating lncRNAs exist in plants, their functional characterization is at an initial stage. By screening an Arabidopsis thaliana lncRNA custom-made array we identified CDF5 LONG NONCODING RNA (FLORE), a circadian-regulated lncRNA that is a NAT of CDF5...
July 31, 2017: New Phytologist
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