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mRNA degradation

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https://www.readbyqxmd.com/read/29153837/a-method-for-the-acute-and-rapid-degradation-of-endogenous-proteins
#1
Dean Clift, William A McEwan, Larisa I Labzin, Vera Konieczny, Binyam Mogessie, Leo C James, Melina Schuh
Methods for the targeted disruption of protein function have revolutionized science and greatly expedited the systematic characterization of genes. Two main approaches are currently used to disrupt protein function: DNA knockout and RNA interference, which act at the genome and mRNA level, respectively. A method that directly alters endogenous protein levels is currently not available. Here, we present Trim-Away, a technique to degrade endogenous proteins acutely in mammalian cells without prior modification of the genome or mRNA...
November 13, 2017: Cell
https://www.readbyqxmd.com/read/29153700/heparanase-expression-in-blood-is-sensitive-to-monitor-response-to-anticancer-treatment-in-pancreatic-cancer-a-pilot-study
#2
Wujun Wu, Lin Zhao, Yongtian Yu, Haitian Hu, Huaiping Shi, Qian'an Jia, Lixue Du
BACKGROUND: /Objectives: High heparanase level was shown in maliganant tumor; however, whether or not heparanase may serve as a sensitive marker to monitor response to anticancer treatment is still unknown. METHODS: In the pilot study, heparanase mRNA expression in peripheral blood mononuclear cell fraction (PBMC) and activity in plasma and urine were detected by quantitative real time RT-PCR and heparan-degrading enzyme assay in 31 pancreatic cancer patients. RESULTS: Heparanase mRNA and activity in samples from cancer patients were significantly higher than that in healthy donors...
November 13, 2017: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/29152905/the-gait-translational-control-system
#3
REVIEW
Abul Arif, Peng Yao, Fulvia Terenzi, Jie Jia, Partho Sarothi Ray, Paul L Fox
The interferon (IFN)-γ-activated inhibitor of translation (GAIT) system directs transcript-selective translational control of functionally related genes. In myeloid cells, IFN-γ induces formation of a multiprotein GAIT complex that binds structural GAIT elements in the 3'-untranslated regions (UTRs) of multiple inflammation-related mRNAs, including ceruloplasmin and VEGF-A, and represses their translation. The human GAIT complex is a heterotetramer containing glutamyl-prolyl tRNA synthetase (EPRS), NS1-associated protein 1 (NSAP1), ribosomal protein L13a (L13a), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH)...
November 20, 2017: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/29150959/nono-ubiquitination-is-mediated-by-fbw7-and-gsk3-%C3%AE-via-a-degron-lost-upon-chromosomal-rearrangement-in-cancer
#4
Luigi Alfano, Antonella Caporaso, Angela Altieri, Caterina Costa, Iris M Forte, Carmelina A Iannuzzi, Daniela Barone, Luca Esposito, Antonio Giordano, Francesca Pentimalli
NONO is an RNA-binding protein involved in transcription, mRNA splicing, DNA repair and checkpoint activation in response to UV radiation. NONO expression has been found altered in several tumour types, including prostate, colon, breast, melanoma and in papillary renal carcinoma, in which an X chromosome inversion generates a NONO-TFE3 fusion protein. Upon such rearrangement, NONO loses its C-terminal domain. Through bioinformatics analysis, we identified a putative degron motif, known to be recognized by the Skp1-Cul1-F-box-protein (SCF) complex...
November 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29150439/suppression-of-fip200-and-autophagy-by-tumor-derived-lactate-promotes-na%C3%A3-ve-t-cell-apoptosis-and-affects-tumor-immunity
#5
Houjun Xia, Wei Wang, Joel Crespo, Ilona Kryczek, Wei Li, Shuang Wei, Zhaoqun Bian, Tomasz Maj, Mingxiao He, Rebecca J Liu, Youwen He, Ramandeep Rattan, Adnan Munkarah, Jun-Lin Guan, Weiping Zou
Naïve T cells are poorly studied in cancer patients. We report that naïve T cells are prone to undergo apoptosis due to a selective loss of FAK family-interacting protein of 200 kDa (FIP200) in ovarian cancer patients and tumor-bearing mice. This results in poor antitumor immunity via autophagy deficiency, mitochondria overactivation, and high reactive oxygen species production in T cells. Mechanistically, loss of FIP200 disables the balance between proapoptotic and antiapoptotic Bcl-2 family members via enhanced argonaute 2 (Ago2) degradation, reduced Ago2 and microRNA1198-5p complex formation, less microRNA1198-5p maturation, and consequently abolished microRNA1198-5p-mediated repression on apoptotic gene Bak1 Bcl-2 overexpression and mitochondria complex I inhibition rescue T cell apoptosis and promoted tumor immunity...
November 17, 2017: Science Immunology
https://www.readbyqxmd.com/read/29149987/inhibition-of-porcine-endogenous-retrovirus-by-multi-targeting-micro-rna-against-long-terminal-region
#6
H-C Chung, V-G Nguyen, W-T Oh, T-M-L Huynh, H-J Moon, J-H Lee, H-K Kim, S-J Park, B-K Park
BACKGROUND: There might be much benefit in xenotransplantation, however, the risk of infections across species barriers remains, especially porcine endogenous retrovirus (PERV). To date, many attempts have been made to knock down active PERVs by inhibitory RNA (RNAi) and micro RNA (miRNA), which target different genes of PERV. There are a few studies that have explored whether targeting promoter regions of PERV could exert an inhibition effect. METHODS: miRNAs were automatically selected based on an online program BLOCK-iT RNAi Designer...
November 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/29148754/eurycomalactone-inhibits-expression-of-endothelial-adhesion-molecules-at-a-post-transcriptional-level
#7
Clemens Malainer, Daniel Schachner, Enrico Sangiovanni, Atanas G Atanasov, Stefan Schwaiger, Hermann Stuppner, Elke H Heiss, Verena M Dirsch
The C-19 quassinoid eurycomalactone (1) has recently been shown to be a potent (IC50 = 0.5 μM) NF-κB inhibitor in a luciferase reporter model. In this study, we show that 1 with similar potency inhibited the expression of the NF-κB-dependent target genes ICAM-1, VCAM-1, and E-selectin in TNFα-activated human endothelial cells (HUVECtert) by flow cytometry experiments. Surprisingly, 1 (2 μM) did not inhibit TNFα-induced IKKα/β or IκBα phosphorylation significantly. Also, the TNFα-induced degradation of IκBα remained unchanged in response to 1 (2 μM)...
November 17, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/29143548/evaluation-on-the-thyroid-disrupting-mechanism-of-malathion-in-fischer-rat-thyroid-follicular-cell-line-frtl-5
#8
Jingyuan Xiong, Liantian Tian, Yongjie Qiu, Ding Sun, Hao Zhang, Mei Wu, Jintao Wang
Thyroid hormones are involved in many important physiological activities including regulation of energy metabolism, development of nervous system, maintenance of cerebral functions, and so on. Endocrine-disrupting chemicals (EDCs) that interfere with thyroid functions raise serious concerns due to their frequent misuse in areas where regulations are poorly implemented. In addition, chemicals that are originally regarded safe may now be considered as toxic with the development of life sciences. Malathion is an organophosphate insecticide that is widely applied and distributed in agricultural and residential settings...
November 16, 2017: Drug and Chemical Toxicology
https://www.readbyqxmd.com/read/29142209/fbxo4-mediated-degradation-of-fxr1-suppresses-tumorigenesis-in-head-and-neck-squamous-cell-carcinoma
#9
Shuo Qie, Mrinmoyee Majumder, Katarzyna Mackiewicz, Breege V Howley, Yuri K Peterson, Philip H Howe, Viswanathan Palanisamy, J Alan Diehl
The Fbxo4 tumour suppressor is a component of an Skp1-Cul1-F-box E3 ligase for which two substrates are known. Here we show purification of SCF(Fbxo4) complexes results in the identification of fragile X protein family (FMRP, Fxr1 and Fxr2) as binding partners. Biochemical and functional analyses reveal that Fxr1 is a direct substrate of SCF(Fbxo4). Consistent with a substrate relationship, Fxr1 is overexpressed in Fbxo4 knockout cells, tissues and in human cancer cells, harbouring inactivating Fbxo4 mutations...
November 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/29141136/systemic-mrna-delivery-to-the-lungs-by-functional-polyester-based-carriers
#10
Yunfeng Yan, Hu Xiong, Xinyi Zhang, Qiang Cheng, Daniel John Siegwart
Messenger RNA (mRNA) has recently come into focus as an emerging therapeutic class with great potential for protein replacement therapy, cancer immunotherapy, regenerative medicine, vaccines, and gene editing. However, the lack of effective and safe delivery methods impedes the broad application of mRNA-based therapeutics. Here, we report a robust approach to develop efficient polymeric delivery carriers for mRNA. Lead polyesters were identified by in vitro screening of a 480-member combinatorially modified poly(trimethylolpropane allyl ether-co-suberoyl chloride) library for the delivery of luciferase encoding mRNA (Luc mRNA) to IGROV1 cells...
November 15, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/29138805/extracellular-polysaccharides-purified-from-aureobasidium-pullulans-sm%C3%A2-2001-polycan-inhibit-dexamethasone%C3%A2-induced-muscle-atrophy-in-mice
#11
Jong-Min Lim, Young Joon Lee, Hyung-Rae Cho, Dong-Chan Park, Go-Woon Jung, Sae Kwang Ku, Jae-Suk Choi
The present study assessed the beneficial skeletal muscle‑preserving effects of extracellular polysaccharides from Aureobasidium pullulans SM‑2001 (Polycan) (EAP) on dexamethasone (DEXA)‑induced catabolic muscle atrophy in mice. To investigate whether EAP prevented catabolic DEXA‑induced muscle atrophy, and to examine its mechanisms of action, EAP (100, 200 and 400 mg/kg) was administered orally, once a day for 24 days. EAP treatment was initiated 2 weeks prior to DEXA treatment (1 mg/kg, once a day for 10 days) in mice...
November 10, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29137669/blocked-expression-of-key-genes-of-the-angiogenic-pathway-in-jsrv-induced-pulmonary-adenocarcinomas
#12
Maryline Gomes, Fabienne Archer, Nicolas Girard, Barbara Gineys, Christine Dolmazon, Alexandra Bobet Erny, Jean-François Mornex, Caroline Leroux
JSRV (Jaagsiekte Sheep Retrovirus) is a retrovirus inducing a transmissible lung adenocarcinoma in sheep and goats with predominantly lepidic and papillary lesions. This naturally occurring lung cancer in large animals shares many features with human pneumonic-type lung adenocarcinomas with predominant lepidic growth. The metastatic spread is rare in both human and animal cancers. This unique feature prompted us to decipher the angiogenesis pathway in these cancers. We focused on the levels of mRNA and proteins of genes implicated in the extension of JSRV-induced lung adenocarcinomas by studying their expression in lung cancers (n = 10) and normal lungs (n = 10) and in primary epithelial alveolar type II cells derived from cancers (n = 10) or normal lungs (n = 6)...
November 14, 2017: Veterinary Research
https://www.readbyqxmd.com/read/29137610/hemoglobin-stimulates-the-expression-of-adamts-5-and-adamts-9-by-synovial-cells-a-possible-cause-of-articular-cartilage-damage-after-intra-articular-hemorrhage
#13
Takuya Tajima, Tomohisa Sekimoto, Nami Yamaguchi, Noboru Taniguchi, Syuji Kurogi, Masugi Maruyama, Etsuo Chosa
BACKGROUND: ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs) proteins play an important pathological role in matrix degeneration. Aggrecan degradation is a significant and critical event in early-stage osteoarthritis. To determine the effect of hemoglobin (Hb) on the ability of synovial tissues to produce ADAMTS family members, we examined the influence of Hb by synovial cells in an in vitro experimental system. METHODS: Synovial tissues were obtained from five young patients with meniscal injury under arthroscopic surgery...
November 14, 2017: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/29134393/metatranscriptomics-reveals-the-hydrolytic-potential-of-peat-inhabiting-planctomycetes
#14
Anastasia A Ivanova, Carl-Eric Wegner, Yongkyu Kim, Werner Liesack, Svetlana N Dedysh
Members of the phylum Planctomycetes are common inhabitants of northern Sphagnum-dominated wetlands. Evidence is accumulating that, in these environments, some planctomycetes may be involved in degrading polymeric organic matter. The experimental data, however, remain scarce due to the low number of characterized representatives of this phylum. In a previous study, we used metatranscriptomics to assess the activity response of peat-inhabiting microorganisms to biopolymers abundantly present in native peat. The community responses to cellulose, xylan, pectin, and chitin availability were analysed relative to unamended controls...
November 13, 2017: Antonie Van Leeuwenhoek
https://www.readbyqxmd.com/read/29133892/er-associated-degradation-regulates-alzheimer-s-amyloid-pathology-and-memory-function-by-modulating-%C3%AE-secretase-activity
#15
Bing Zhu, LuLin Jiang, Timothy Huang, Yingjun Zhao, Tongfei Liu, Yongwang Zhong, Xiaoguang Li, Alexandre Campos, Kenneth Pomeroy, Eliezer Masliah, Dongxian Zhang, Huaxi Xu
Endoplasmic-reticulum-associated degradation (ERAD) is an important protein quality control system which maintains protein homeostasis. Constituents of the ERAD complex and its role in neurodegeneration are not yet fully understood. Here, using proteomic and FRET analyses, we demonstrate that the ER protein membralin is an ERAD component, which mediates degradation of ER luminal and membrane substrates. Interestingly, we identify nicastrin, a key component of the γ-secretase complex, as a membralin binding protein and membralin-associated ERAD substrate...
November 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29133129/hbsag-mrna-degradation-induced-by-dihydroquinolizinone-molecule-depends-on-hbv-posttranscriptional-regulatory-element
#16
Tianlun Zhou, Timothy Block, Fei Liu, Andrew S Kondratowicz, Liren Sun, Siddhartha Rawat, Jeffrey Branson, Fang Guo, Hongyan Liang, Lauren Bailey, Chris Moore, Xiaohe Wang, Andy Cuconatti, Min Gao, Amy C H Lee, Troy Harasym, Tim Chiu, Dimitar Gotchev, Bruce Dorsey, Rene Rijnbrand, Michael J Sofia
In pursuit of novel therapeutics targeting the hepatitis B virus (HBV) infection, we evaluated a dihydroquinolizinone compound (DHQ-1) that possessed nanomolar activities against the production of virion and surface protein (HBsAg) in tissue culture. This compound also showed broad HBV genotype coverage and was inactive against a panel of DNA and RNA viruses of other species. Oral administration of DHQ-1 in the AAV-HBV mouse model resulted in a strong reduction of serum HBsAg as soon as 4 days following the commencement of treatment...
November 10, 2017: Antiviral Research
https://www.readbyqxmd.com/read/29131268/correlation-of-insulin-like-growth-factor-1-and-osteoarthritic-cartilage-degradation-a-spontaneous-osteoarthritis-in-guinea-pig
#17
F-Y Wei, J K Lee, L Wei, F Qu, J-Z Zhang
OBJECTIVE: The pathogenesis of osteoarthritis centers on the imbalance between catabolic and anabolic processes in cartilage metabolism. Insulin growth factor 1 (IGF-1) has been shown to have anabolic effects in cartilage in vitro. This study aim to determine whether IGF-1 on cartilage is associated with loss of chondrocyte and extracellular matrix breakdown using the Hartley guinea pig model. MATERIALS AND METHODS: Cartilage from the medial and lateral tibial plateau of 6-month and 12-month old Hartley guinea pigs were used for this study...
October 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29131164/an-improved-ms2-system-for-accurate-reporting-of-the-mrna-life-cycle
#18
Evelina Tutucci, Maria Vera, Jeetayu Biswas, Jennifer Garcia, Roy Parker, Robert H Singer
The MS2-MCP system enables researchers to image multiple steps of the mRNA life cycle with high temporal and spatial resolution. However, for short-lived mRNAs, the tight binding of the MS2 coat protein (MCP) to the MS2 binding sites (MBS) protects the RNA from being efficiently degraded, and this confounds the study of mRNA regulation. Here, we describe a reporter system (MBSV6) with reduced affinity for the MCP, which allows mRNA degradation while preserving single-molecule detection determined by single-molecule FISH (smFISH) or live imaging...
November 13, 2017: Nature Methods
https://www.readbyqxmd.com/read/29131148/structure-guided-chemical-modification-of-guide-rna-enables-potent-non-viral-in-vivo-genome-editing
#19
Hao Yin, Chun-Qing Song, Sneha Suresh, Qiongqiong Wu, Stephen Walsh, Luke Hyunsik Rhym, Esther Mintzer, Mehmet Fatih Bolukbasi, Lihua Julie Zhu, Kevin Kauffman, Haiwei Mou, Alicia Oberholzer, Junmei Ding, Suet-Yan Kwan, Roman L Bogorad, Timofei Zatsepin, Victor Koteliansky, Scot A Wolfe, Wen Xue, Robert Langer, Daniel G Anderson
Efficient genome editing with Cas9-sgRNA in vivo has required the use of viral delivery systems, which have limitations for clinical applications. Translational efforts to develop other RNA therapeutics have shown that judicious chemical modification of RNAs can improve therapeutic efficacy by reducing susceptibility to nuclease degradation. Guided by the structure of the Cas9-sgRNA complex, we identify regions of sgRNA that can be modified while maintaining or enhancing genome-editing activity, and we develop an optimal set of chemical modifications for in vivo applications...
November 13, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/29129636/inflammation-mediated-muscle-metabolic-dysregulation-local-and-remote-to-the-site-of-major-abdominal-surgery
#20
Krishna K Varadhan, Dumitru Constantin-Teodosiu, Despina Constantin, Paul L Greenhaff, Dileep N Lobo
BACKGROUND & AIMS: Postoperative hyperglycaemia is common in patients having major surgery and is associated with adverse outcomes. This study aimed to determine whether bacteraemia contributed to postoperative systemic inflammation, and whether increases in the expression of muscle mRNAs and proteins reflecting increased muscle inflammation, atrophy and impaired carbohydrate oxidation were evident at the time of surgery, and both local and distant to the site of trauma, and could be associated with impaired glucoregulation...
November 2, 2017: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
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