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Antisense protein

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https://www.readbyqxmd.com/read/29341839/activation-of-frataxin-protein-expression-by-antisense-oligonucleotides-targeting-the-mutant-expanded-repeat
#1
Liande Li, Xiulong Shen, Zhongtian Liu, Michaela Norrbom, Thazha P Prakash, Daniel O'Reilly, Vivek K Sharma, Masad J Damha, Jonathan K Watts, Frank Rigo, David R Corey
Friedreich's Ataxia (FA) is an inherited neurologic disorder caused by an expanded GAA repeat within intron 1 of the frataxin (FXN) gene that reduces expression of FXN protein. Agents that increase expression of FXN have the potential to alleviate the disease. We previously reported that duplex RNAs (dsRNAs) and antisense oligonucleotides (ASOs) complementary to the GAA repeat could enhance expression of FXN protein. We now explore the potential of a diverse group of chemically modified dsRNAs and ASOs to define the breadth of repeat-targeted synthetic nucleic acids as a platform for therapeutic development for FA...
January 17, 2018: Nucleic Acid Therapeutics
https://www.readbyqxmd.com/read/29341438/natural-antisense-transcripts-in-diseases-from-modes-of-action-to-targeted-therapies
#2
REVIEW
Elżbieta Wanowska, Magdalena Regina Kubiak, Wojciech Rosikiewicz, Izabela Makałowska, Michał Wojciech Szcześniak
Antisense transcription is a widespread phenomenon in mammalian genomes, leading to production of RNAs molecules referred to as natural antisense transcripts (NATs). NATs apply diverse transcriptional and post-transcriptional regulatory mechanisms to carry out a wide variety of biological roles that are important for the normal functioning of living cells, but their dysfunctions can be associated with human diseases. In this review, we attempt to provide a molecular basis for the involvement of NATs in the etiology of human disorders such as cancers and neurodegenerative and cardiovascular diseases...
January 17, 2018: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/29339785/the-lncrna-gata6-as-epigenetically-regulates-endothelial-gene-expression-via-interaction-with-loxl2
#3
Philipp Neumann, Nicolas Jaé, Andrea Knau, Simone F Glaser, Youssef Fouani, Oliver Rossbach, Marcus Krüger, David John, Albrecht Bindereif, Phillip Grote, Reinier A Boon, Stefanie Dimmeler
Impaired or excessive growth of endothelial cells contributes to several diseases. However, the functional involvement of regulatory long non-coding RNAs in these processes is not well defined. Here, we show that the long non-coding antisense transcript of GATA6 (GATA6-AS) interacts with the epigenetic regulator LOXL2 to regulate endothelial gene expression via changes in histone methylation. Using RNA deep sequencing, we find that GATA6-AS is upregulated in endothelial cells during hypoxia. Silencing of GATA6-AS diminishes TGF-β2-induced endothelial-mesenchymal transition in vitro and promotes formation of blood vessels in mice...
January 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29339778/a-novel-human-muscle-cell-model-of-duchenne-muscular-dystrophy-created-by-crispr-cas9-and-evaluation-of-antisense-mediated-exon-skipping
#4
Takenori Shimo, Kana Hosoki, Yusuke Nakatsuji, Toshifumi Yokota, Satoshi Obika
Oligonucleotide-mediated splicing modulation is a promising therapeutic approach for Duchenne muscular dystrophy (DMD). Recently, eteplirsen, a phosphorodiamidate morpholino oligomer-based splice-switching oligonucleotide (SSO) targeting DMD exon 51, was approved by the U.S. Food and Drug Administration as the first antisense-based drug for DMD patients. For further exploring SSOs targeting other exons in the DMD gene, the efficacy of exon skipping and protein rescue with each SSO sequence needs evaluations in vitro...
January 16, 2018: Journal of Human Genetics
https://www.readbyqxmd.com/read/29337064/cloning-and-functional-characterization-of-a-p-coumaroyl-quinate-shikimate-3-hydroxylase-from-potato-solanum-tuberosum
#5
Benjamin J Knollenberg, Jingjing Liu, Shu Yu, Hong Lin, Li Tian
Chlorogenic acid (CGA) plays an important role in protecting plants against pathogens and promoting human health. Although CGA accumulates to high levels in potato tubers, the key enzyme p-coumaroyl quinate/shikimate 3'-hydroxylase (C3'H) for CGA biosynthesis has not been isolated and functionally characterized in potato. In this work, we cloned StC3'H from potato and showed that it catalyzed the formation of caffeoylshikimate and CGA (caffeoylquinate) from p-coumaroyl shikimate and p-coumaroyl quinate, respectively, but was inactive towards p-coumaric acid in in vitro enzyme assays...
January 11, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29335299/hotair-contributes-to-cell-proliferation-and-metastasis-of-cervical-cancer-via-targeting-mir-23b-mapk1-axis
#6
Qin Li, Yanhong Feng, Xu Chao, Shuai Shi, Man Liang, Yumei Qiao, Bin Wang, Pin Wang, Zhenning Zhu
The long non-coding RNA HOX transcript antisense RNA (HOTAIR) has been found overexpressed in many human malignancies and involved in tumor progression and metastasis. Although the downstream target through which HOTAIR modulates tumor metastasis is not well-known, evidence suggests that microRNA23b (miR23b) might be involved in this event. In the present study, the expressions of HOTAIR and miR23b were detected by real-time PCR in 33 paired cervical cancer tissue samples and cervical cell lines. The effects of HOTAIR on the expressions of miR23b and mitogen-activated protein kinase 1 (MAPK1) were studied by overexpression and RNA interference approaches...
January 15, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29334995/antisense-suppression-of-the-nonsense-mediated-decay-factor-upf3b-as-a-potential-treatment-for-diseases-caused-by-nonsense-mutations
#7
Lulu Huang, Audrey Low, Sagar S Damle, Melissa M Keenan, Steven Kuntz, Susan F Murray, Brett P Monia, Shuling Guo
BACKGROUND: About 11% of all human genetic diseases are caused by nonsense mutations that generate premature translation termination codons (PTCs) in messenger RNAs (mRNA). PTCs not only lead to the production of truncated proteins, but also often result in  decreased mRNA abundance due to  nonsense-mediated mRNA decay (NMD). Although pharmacological inhibition of NMD could be an attractive therapeutic approach for the treatment of diseases caused by nonsense mutations, NMD also regulates the expression of 10-20% of the normal transcriptome...
January 15, 2018: Genome Biology
https://www.readbyqxmd.com/read/29334984/new-insights-into-angplt3-in-controlling-lipoprotein-metabolism-and-risk-of-cardiovascular-diseases
#8
REVIEW
Xin Su, Dao-Quan Peng
Dyslipidemia, characterized by elevation of plasma low density lipoprotein cholesterol (LDL-C), triglyceride (TG) and reduction of plasma high density lipoprotein cholesterol (HDL-C), has been verified as a causal risk factor for cardiovascular diseases (CVD), leading to a high mortality rate in general population. It is important to understand the molecular metabolism underlying dyslipidemia in order to reduce the risk and to develop effective therapeutic approaches against CVD. ANGPTL3 (human) or Angptl3 (mouse), one member of the angiopoietin-like protein (ANGPTL) family, has been identified as an important regulator of lipid metabolism by inhibiting LPL and EL activity...
January 15, 2018: Lipids in Health and Disease
https://www.readbyqxmd.com/read/29331925/overexpression-of-chrysanthemum-lavandulifolium-clcbf1-in-chrysanthemum-morifolium-white-snow-improves-the-level-of-salinity-and-drought-tolerance
#9
Wenjie Gao, Miao He, Jie Liu, Xin Ma, Yu Zhang, Silan Dai, Yunwei Zhou
This paper reports the first study on plant CBF transcription factors (TF) in salt and drought stress responses in Chrysanthemum lavandulifolium. A CBF homolog gene, named as ClCBF1, from C. lavandulifolium was isolated using rapid amplification of cDNA ends (RACE). The deduced peptide is comprised of 210 amino acids (AA) containing an AP2 structural domain characteristic of the AP2 gene family. Quantitative real-time PCR revealed that ClCBF1 gene exhibit differential expression patterns across root, leaf and stem tissues, and it was strongly induced under salt and drought treatments of C...
January 8, 2018: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/29331923/cold-regulated-protein-slcor413im1-confers-chilling-stress-tolerance-in-tomato-plants
#10
Xiaocui Ma, Chong Chen, Minmin Yang, Xinchun Dong, Wei Lv, Qingwei Meng
Chilling stress severely affects the growth, development and productivity of crops. Chloroplast, a photosynthesis site, is extremely sensitive to chilling stress. In this study, the functions of a gene encoding a cold-regulated protein (SlCOR413IM1) under chilling stress were investigated using sense and antisense transgenic tomatoes. Under chilling stress, SlCOR413IM1 expression was rapidly induced and the sense lines exhibited better growth state of seedlings and grown tomato plants. Overexpression of SlCOR413IM1 alleviated chilling-induced damage to the chloroplast membrane and structure, whereas suppression of SlCOR413IM1 aggravated the damage to chloroplast...
January 5, 2018: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/29328475/heat-shock-protein-27-knockdown-using-nucleotide%C3%A2-based-therapies-enhances-sensitivity-to-5-fu-chemotherapy-in-sw480-human-colon-cancer-cells
#11
Takehiro Shimada, Masashi Tsuruta, Hirotoshi Hasegawa, Koji Okabayashi, Kohei Shigeta, Takashi Ishida, Yusuke Asada, Hirofumi Suzumura, Kaoru Koishikawa, Shingo Akimoto, Yuko Kitagawa
Heat shock protein 27 (Hsp27) is a chaperone protein of low molecular weight that is produced in response to various stresses and has a cytoprotective function. In the present study we found that there is a strong correlation between sensitivity to 5-fluorouracil (5-FU) and the expression of Hsp27 in colorectal cancer. Apatorsen is an antisense oligonucleotide that targets Hsp27 and has various antitumor effects in some types of cancer, such as bladder and prostate. Although several clinical studies are currently studying apatorsen in many malignancies, to date no promising results have been reported for colorectal cancer...
January 3, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29327679/natural-and-artificial-strategies-to-control-the-conjugative-transmission-of-plasmids
#12
María Getino, Fernando de la Cruz
Conjugative plasmids are the main carriers of transmissible antibiotic resistance (AbR) genes. For that reason, strategies to control plasmid transmission have been proposed as potential solutions to prevent AbR dissemination. Natural mechanisms that bacteria employ as defense barriers against invading genomes, such as restriction-modification or CRISPR-Cas systems, could be exploited to control conjugation. Besides, conjugative plasmids themselves display mechanisms to minimize their associated burden or to compete with related or unrelated plasmids...
January 2018: Microbiology Spectrum
https://www.readbyqxmd.com/read/29326059/differential-requirement-of-de-novo-arc-protein-synthesis-in-the-insular-cortex-and-the-amygdala-for-safe-and-aversive-taste-long-term-memory-formation
#13
Guzmán-Ramos Kioko, Venkataraman Archana, Morin Jean-Pascal, Osorio-Gómez Daniel, Bermúdez-Rattoni Federico
Several immediate early genes products are known to be involved in the facilitation of structural and functional modifications at distinct synapses activated through experience. The IEG-encoded protein Arc (activity regulated cytoskeletal-associated protein) has been widely implicated in long-term memory formation and stabilization. In this study, we sought to evaluate a possible role for de novo Arc protein synthesis in the insular cortex (IC) and in the amygdala (AMY) during long-term taste memory formation...
January 8, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29324704/dissection-of-myogenic-differentiation-signatures-in-chickens-by-rna-seq-analysis
#14
Tingting Li, Genxi Zhang, Pengfei Wu, Lian Duan, Guohui Li, Qiuhong Liu, Jinyu Wang
A series of elaborately regulated and orchestrated changes in gene expression profiles leads to muscle growth and development. In this study, RNA sequencing was used to profile embryonic chicken myoblasts and fused myotube transcriptomes, long non-coding RNAs (lncRNAs), and messenger RNAs (mRNAs) at four stages of myoblast differentiation. Of a total of 2484 lncRNA transcripts, 2288 were long intergenic non-coding RNAs (lincRNAs) and 198 were antisense lncRNAs. Additionally, 1530 lncRNAs were neighboring 2041 protein-coding genes (<10 kb upstream and downstream) and functionally enriched in several pathways related to skeletal muscle development that have been extensively studied, indicating that these genes may be in cis-regulatory relationships...
January 11, 2018: Genes
https://www.readbyqxmd.com/read/29323740/long-non-coding-rna-asbel-promotes-osteosarcoma-cell-proliferation-migration-and-invasion-by-regulating-microrna-21
#15
Jianhui Zhao, Zhongli Gao, Chao Zhang, Han Wu, Rui Gu, Rui Jiang
Osteosarcoma is the most common malignant bone tumor in children and adolescents with high rate of incidence, high frequency of recurrence and high degree of metastasis. This study aimed to investigate the effects of long noncoding RNA antisense ncRNA in the Abundant in neuroepithelium area (ANA)/B-cell translocation gene 3 (BTG3) locus (lncRNA ASBEL) on the pathogenesis of osteosarcoma. The expression levels of ASBEL in human osteoblast cells and human osteosarcoma cells were evaluated using qRT-PCR. Effects of ASBEL knockdown on cell viability, migration and invasion were detected using trypan blue exclusion assay, cell migration and invasion assay, respectively...
January 11, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29323119/cug-initiation-and-frameshifting-enable-production-of-dipeptide-repeat-proteins-from-als-ftd-c9orf72-transcripts
#16
Ricardos Tabet, Laure Schaeffer, Fernande Freyermuth, Melanie Jambeau, Michael Workman, Chao-Zong Lee, Chun-Chia Lin, Jie Jiang, Karen Jansen-West, Hussein Abou-Hamdan, Laurent Désaubry, Tania Gendron, Leonard Petrucelli, Franck Martin, Clotilde Lagier-Tourenne
Expansion of G4C2 repeats in the C9ORF72 gene is the most prevalent inherited form of amyotrophic lateral sclerosis and frontotemporal dementia. Expanded transcripts undergo repeat-associated non-AUG (RAN) translation producing dipeptide repeat proteins from all reading frames. We determined cis-factors and trans-factors influencing translation of the human C9ORF72 transcripts. G4C2 translation operates through a 5'-3' cap-dependent scanning mechanism, requiring a CUG codon located upstream of the repeats and an initiator Met-tRNAMeti...
January 11, 2018: Nature Communications
https://www.readbyqxmd.com/read/29316906/the-function-of-tcf3-in-medaka-embryos-efficient-knockdown-with-pepnas
#17
Gerlinde Doenz, Sebastian Dorn, Narges Aghaallaei, Baubak Bajoghli, Elisabeth Riegel, Michaela Aigner, Holger Bock, Birgit Werner, Thomas Lindhorst, Thomas Czerny
BACKGROUND: The application of antisense molecules, such as morpholino oligonucleotides, is an efficient method of gene inactivation in vivo. We recently introduced phosphonic ester modified peptide nucleic acids (PNA) for in vivo loss-of-function experiments in medaka embryos. Here we tested novel modifications of the PNA backbone to knockdown the medaka tcf3 gene. RESULTS: A single tcf3 gene exists in the medaka genome and its inactivation strongly affected eye development of the embryos, leading to size reduction and anophthalmia in severe cases...
January 9, 2018: BMC Biotechnology
https://www.readbyqxmd.com/read/29316633/investigation-of-new-morpholino-oligomers-to-increase-survival-motor-neuron-protein-levels-in-spinal-muscular-atrophy
#18
Agnese Ramirez, Sebastiano G Crisafulli, Mafalda Rizzuti, Nereo Bresolin, Giacomo P Comi, Stefania Corti, Monica Nizzardo
Spinal muscular atrophy (SMA) is an autosomal-recessive childhood motor neuron disease and the main genetic cause of infant mortality. SMA is caused by deletions or mutations in the survival motor neuron 1 (SMN1) gene, which results in SMN protein deficiency. Only one approved drug has recently become available and allows for the correction of aberrant splicing of the paralogous SMN2 gene by antisense oligonucleotides (ASOs), leading to production of full-length SMN protein. We have already demonstrated that a sequence of an ASO variant, Morpholino (MO), is particularly suitable because of its safety and efficacy profile and is both able to increase SMN levels and rescue the murine SMA phenotype...
January 6, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29311544/silencing-of-the-lncrna-zeb2-nat-facilitates-reprogramming-of-aged-fibroblasts-and-safeguards-stem-cell-pluripotency
#19
Bruno Bernardes de Jesus, Sérgio Pires Marinho, Sara Barros, António Sousa-Franco, Catarina Alves-Vale, Tânia Carvalho, Maria Carmo-Fonseca
Aging imposes a barrier to somatic cell reprogramming through poorly understood mechanisms. Here, we report that fibroblasts from old mice express higher levels of Zeb2, a transcription factor that activates epithelial-to-mesenchymal transition. Synthesis of Zeb2 protein is controlled by a natural antisense transcript named Zeb2-NAT. We show that transfection of adult fibroblasts with specific LNA Gapmers induces a robust downregulation of Zeb2-NAT transcripts and Zeb2 protein and enhances the reprogramming of old fibroblasts into pluripotent cells...
January 8, 2018: Nature Communications
https://www.readbyqxmd.com/read/29311362/novel-transcriptional-activity-and-extensive-allelic-imbalance-in-the-human-mhc-region
#20
Elizabeth Gensterblum-Miller, Weisheng Wu, Amr H Sawalha
The MHC region encodes HLA genes and is the most complex region in the human genome. The extensively polymorphic nature of the HLA hinders accurate localization and functional assessment of disease risk loci within this region. Using targeted capture sequencing and constructing individualized genomes for transcriptome alignment, we identified 908 novel transcripts within the human MHC region. These include 593 novel isoforms of known genes, 137 antisense strand RNAs, 119 novel long intergenic noncoding RNAs, and 5 transcripts of 3 novel putative protein-coding human endogenous retrovirus genes...
January 8, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
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