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https://www.readbyqxmd.com/read/28813667/human-gw182-paralogs-are-the-central-organizers-for-rna-mediated-control-of-transcription
#1
Jessica A Hicks, Liande Li, Masayuki Matsui, Yongjun Chu, Oleg Volkov, Krystal C Johnson, David R Corey
In the cytoplasm, small RNAs can control mammalian translation by regulating the stability of mRNA. In the nucleus, small RNAs can also control transcription and splicing. The mechanisms for RNA-mediated nuclear regulation are not understood and remain controversial, hindering the effective application of nuclear RNAi and investigation of its natural regulatory roles. Here, we reveal that the human GW182 paralogs TNRC6A/B/C are central organizing factors critical to RNA-mediated transcriptional activation. Mass spectrometry of purified nuclear lysates followed by experimental validation demonstrates that TNRC6A interacts with proteins involved in protein degradation, RNAi, the CCR4-NOT complex, the mediator complex, and histone-modifying complexes...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28812343/xanthohumol-suppresses-mylip-idol-gene-expression-and-modulates-ldlr-abundance-and-activity-in-hepg2-cells
#2
Shih-Fen Chen, Pei-Yi Chen, Hao-Jen Hsu, Ming-Jiuan Wu, Jui-Hung Yen
Xanthohumol, a prenylated flavonoid found in hops (Humulus lupulus L.), exhibits multiple biological activities such as anti-atherosclerosis and hypolipidemic activities. In this study, we aim to investigate the hypocholesterolemic effects and molecular mechanisms of xanthohumol in hepatic cells. We found that xanthohumol (10 and 20 μM) increased the amount of cell-surface low-density lipoprotein receptor (LDLR) from 100.0 ± 2.1% to 115.0±1.3% and 135.2±2.7%, and enhanced the LDL uptake activity from 100...
August 16, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28811753/characterization-of-the-rosellinia-necatrix-transcriptome-and-genes-related-to-pathogenesis-by-single-molecule-mrna-sequencing
#3
Hyeongmin Kim, Seung Jae Lee, Ick-Hyun Jo, Jinsu Lee, Wonsil Bae, Hyemin Kim, Kyungho Won, Tae Kyung Hyun, Hojin Ryu
White root rot disease, caused by the pathogen Rosellinia necatrix, is one of the world's most devastating plant fungal diseases and affects several commercially important species of fruit trees and crops. Recent global outbreaks of R. necatrix and advances in molecular techniques have both increased interest in this pathogen. However, the lack of information regarding the genomic structure and transcriptome of R. necatrix has been a barrier to the progress of functional genomic research and the control of this harmful pathogen...
August 2017: Plant Pathology Journal
https://www.readbyqxmd.com/read/28811357/autophagy-attenuates-endothelial-to-mesenchymal-transition-by-promoting-snail-degradation-in-human-cardiac-microvascular-endothelial-cells
#4
Jin Zou, Yanhua Liu, Bingong Li, Zeqi Zheng, Xuan Ke, Yanqin Hao, Xuelian Li, Xingxing Li, Fuyou Liu, Zhiyong Zhang
Endothelial-to-mesenchymal transition (EndMT) mainly exists in cardiovascular development and disease progression, and is well known to contribute to cardiac fibrosis. Recent studies indicated that autophagy also participates in the regulation of cardiac fibrosis. However, the precise role of autophagy in cardiac fibrosis and the underlying molecular mechanism remain unclear. This study aimed to explore the role of autophagy in EndMT, reveal the underlying molecular mechanism and seek new therapy for cardiac fibrosis...
August 15, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28810605/microrna-19a-promotes-nasopharyngeal-carcinoma-by-targeting-transforming-growth-factor-%C3%AE-receptor-2
#5
Fang Ma, Zhiyuan Wang, Jingjing Wang, Xianling Liu, Chunhong Hu
MicroRNA (miR), a class of small non-coding RNA, function as key regulators in gene expression through directly binding to the 3' untranslated region of their target mRNA, which further leads to translational repression or mRNA degradation. miR-19a, a member of miR-17-92 cluster, has an oncogenic role in a variety of malignant tumors. However, the exact role of miR-19a in nasopharyngeal carcinoma (NPC) has not previously been studied. The present study aimed to investigate the function and mechanism of miR-19a in regulating the viability and invasion of NPC cells...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28810585/glutamine-promotes-hsp70-and-inhibits-%C3%AE-synuclein-accumulation-in-pheochromocytoma-pc12-cells
#6
Haiyang Wang, Chongyang Tang, Zhenfeng Jiang, Xiao Zhou, Jianhang Chen, Meng Na, Hong Shen, Zhiguo Lin
Hsp70 regulates α-Synuclein (α-Syn) degeneration in Parkinson's disease (PD), indicating that Hsp70 promotion may be able to prevent or reverse α-Syn-induced toxicity in PD. Additionally, it has been demonstrated that glutamine (Gln) enhances Hsp70 expression. In the present study, Gln-induced Hsp70 promotion in pheochromocytoma was investigated with reverse transcription- quantitative polymerase chain reaction and western blotting methods. Then it was observed whether heat shock factor (HSF)-1 was required for this phenomenon with an RNA interference strategy...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28810553/evaluation-of-the-c-domain-of-heparanase-during-age-induced-macrophage-inflammatory-response
#7
Qiaojing Qin, Guang Xu, Weiwei Qi, Mei Guo, Zhaoxia Wang, Wangjie Xu, Zhongdong Qiao, Yong Gu, Jianying Niu
Diabetic vasculopathy is intensified by macrophage inflammation caused by advanced glycation end products (AGEs). Heparanase (HPA) is a unique endoglycosidase, which cleaves heparan sulfate proteoglycans (HSPGs) including syndecan-1 (Syn-1) to further stimulate macrophage cell migration and inflammation. The present study was planned to evaluated the role of C-domain (if any) of HPA in AGE inflammatory response in macrophages. Cell viability was assessed using MTT assay, migration assay, ELISA for tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) levels, mRNA expression by RT-PCR and heparan degrading enzyme assay for HPA activity...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28810544/microrna-9-inhibits-the-proliferation-and-migration-of-malignant-melanoma-cells-via-targeting-sirituin-1
#8
Pingyuan Bu, Chengqun Luo, Quanyong He, Ping Yang, Xi Li, Dan Xu
MicroRNA (miR) are a class of small non-coding RNA that are able to inhibit gene expression by directly binding to the 3' untranslated region (UTR) of their target mRNA and thus promote translational repression or mRNA degradation. Recently, miR-9 was reported to have a suppressive role in malignant melanoma; however, the underlying mechanism remains largely unclear. In the present study, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to examine the mRNA and protein expression levels in malignant melanoma tissues and cell lines...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28808066/maternal-mrnas-with-distinct-3-utrs-define-the-temporal-pattern-of-ccnb1-synthesis-during-mouse-oocyte-meiotic-maturation
#9
Ye Yang, Cai-Rong Yang, Seung Jin Han, Enrico Maria Daldello, Ara Cho, Joao P Sousa Martins, Guoliang Xia, Marco Conti
The final stages of female gamete maturation occur in the virtual absence of transcription, with gene expression driven by a program of selective unmasking, translation, and degradation of maternal mRNAs. Here we demonstrate that the timing of Ccnb1 mRNA translation in mouse oocytes is dependent on the presence of transcripts with different 3' untranslated regions (UTRs). This 3' UTR heterogeneity directs distinct temporal patterns of translational activation or repression. Inclusion or exclusion of cis-acting elements is responsible for these divergent regulations...
July 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28808060/the-human-rna-binding-protein-and-e3-ligase-mex-3c-binds-the-mex-3-recognition-element-mre-motif-with-high-affinity
#10
Lingna Yang, Chongyuan Wang, Fudong Li, Jiahai Zhang, Anam Nayab, Jihui Wu, Yunyu Shi, Qingguo Gong
MEX-3 is a KH domain-containing RNA-binding protein, first identified as a translational repressor in Caenorhabditis elegans, while its four orthologs (MEX-3A-D) in human and mouse were subsequently found to have E3 ubiquitin ligase activity mediated by a RING domain and critical for RNA degradation. Current evidence implicates human MEX-3C in many essential biological processes and suggests a strong connection with immune diseases and carcinogenesis. The highly conserved dual KH domains in MEX-3 proteins enable RNA binding and are essential for the recognition of the 3' UTR and posttranscriptional regulation of MEX-3 target transcripts...
August 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28806398/lysine-52-stabilizes-the-myc-oncoprotein-through-an-scf-fbxw7-independent-mechanism
#11
J De Melo, S S Kim, C Lourenco, L Z Penn
The oncogenic transcription factor c-MYC (MYC) is deregulated and often overexpressed in more than 50% of cancers. MYC deregulation is associated with poor prognosis and aggressive disease, suggesting that the development of therapeutic inhibitors targeting MYC would markedly impact patient outcome. MYC is highly regulated, with a protein and mRNA half-life of ~30 min. The most extensively studied pathway regulating MYC protein stability involves ubiquitylation and proteasomal degradation mediated by the E3-ligase, SCF(Fbxw7)...
August 14, 2017: Oncogene
https://www.readbyqxmd.com/read/28802259/cis-regulatory-elements-explain-most-of-the-mrna-stability-variation-across-genes-in-yeast
#12
Jun Cheng, Kerstin C Maier, Ziga Avsec, Petra Rus, Julien Gagneur
The stability of mRNA is one of the major determinants of gene expression. Although a wealth of sequence elements regulating mRNA stability has been described, their quantitative contributions to half-life are unknown. Here, we built a quantitative model for Saccharomyces cerevisiae based on functional mRNA sequence features that explains 59% of the half-life variation between genes and predicts half-life at a median relative error of 30%. The model revealed a new destabilizing 3'UTR motif, ATATTC, which we functionally validated...
August 11, 2017: RNA
https://www.readbyqxmd.com/read/28801509/exosome-cofactor-hmtr4-competes-with-export-adaptor-alyref-to-ensure-balanced-nuclear-rna-pools-for-degradation-and-export
#13
Jing Fan, Bin Kuai, Guifen Wu, Xudong Wu, Binkai Chi, Lantian Wang, Ke Wang, Zhubing Shi, Heng Zhang, She Chen, Zhisong He, Siyuan Wang, Zhaocai Zhou, Guohui Li, Hong Cheng
The exosome is a key RNA machine that functions in the degradation of unwanted RNAs. Here, we found that significant fractions of precursors and mature forms of mRNAs and long noncoding RNAs are degraded by the nuclear exosome in normal human cells. Exosome-mediated degradation of these RNAs requires its cofactor hMTR4. Significantly, hMTR4 plays a key role in specifically recruiting the exosome to its targets. Furthermore, we provide several lines of evidence indicating that hMTR4 executes this role by directly competing with the mRNA export adaptor ALYREF for associating with ARS2, a component of the cap-binding complex (CBC), and this competition is critical for determining whether an RNA is degraded or exported to the cytoplasm...
August 11, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28800772/endurance-training-lowers-ribosome-density-despite-increasing-ribosome-biogenesis-markers-in-rodent-skeletal-muscle
#14
Matthew A Romero, C Brooks Mobley, Melissa A Linden, Grace Margaret-Eleanor Meers, Jeffrey S Martin, Kaelin C Young, R Scott Rector, Michael D Roberts
OBJECTIVE: The purpose of this study was to examine if: (a) high sugar/high fat Western diet (WD)-feeding affects skeletal muscle ribosome biogenesis markers in hyperphagic, diabetic-prone Otsuka Long-Evans Tokushima Fatty (OLETF) rats, and (b) 12 weeks of treadmill training rescued potential detriments that WD feeding exerted on these markers. METHODS: Eight week-old male OLETF rats were fed a low-fat control diet (O-CON, n = 10) or high/sucrose/cholesterol Western diet (WD)...
August 11, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/28798805/antineuroinflammatory-effects-of-modified-wu-zi-yan-zong-prescription-in-%C3%AE-amyloid-stimulated-bv2-microglia-via-the-nf-%C3%AE%C2%BAb-and-erk-p38-mapk-signaling-pathways
#15
Qian Yu, Fang-Jiao Song, Jin-Feng Chen, Xin Dong, Yong Jiang, Ke-Wu Zeng, Peng-Fei Tu, Xue-Mei Wang
Modified Wu-Zi-Yan-Zong prescription (MWP), a traditional Chinese medicinal decoction, has possessed the neuroprotective and anti-inflammatory properties. The mechanisms associated with these properties, however, are not completely understood. We designed the experiments to elucidate the antineuroinflammatory property of MWP in BV2 microglia activated by β-amyloid (Aβ), which is a characteristic feature of Alzheimer's disease (AD). The composition of MWP was studied using HPLC. BV2 microglia cells were then treated with Aβ in the presence or absence of MWP...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28798419/dna-methylation-of-the-runx2-p1-promoter-mediates-mmp13-transcription-in-chondrocytes
#16
Atsushi Takahashi, María C de Andrés, Ko Hashimoto, Eiji Itoi, Miguel Otero, Mary B Goldring, Richard O C Oreffo
The Runt-related transcription factor 2 (RUNX2) is critical for bone formation as well as chondrocyte maturation. Matrix metalloproteinase (MMP)-13 is a major contributor to cartilage degradation in osteoarthritis (OA). We and others have shown that the abnormal MMP13 gene expression in OA chondrocytes is controlled by changes in the DNA methylation status of specific CpG sites of the proximal promoter, as well as by the actions of different transactivators, including RUNX2. The present study aimed to determine the influence of the methylation status of specific CpG sites in the RUNX2 promoter on RUNX2-driven MMP13 gene expression in OA chondrocytes...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28795162/global-survey-of-mrna-levels-and-decay-rates-of-chlamydia-trachomatis-trachoma-and-lymphogranuloma-venereum-biovars
#17
Rita Ferreira, Vítor Borges, Maria José Borrego, João Paulo Gomes
Interpreting the intricate bacterial transcriptomics implies understanding the dynamic relationship established between de novo transcription and the degradation of transcripts. Here, we performed a comparative overview of gene expression levels and mRNA decay rates for different-biovar (trachoma and lymphogranuloma venereum) strains of the obligate intracellular bacterium Chlamydia trachomatis. By using RNA-sequencing to measure gene expression levels at mid developmental stage and mRNA decay rates upon rifampicin-based transcription blockage, we observed that: i) 60-70% of the top-50 expressed genes encode proteins with unknown function and proteins involved in "Translation, ribosomal structure and biogenesis" for all strains; ii) the expression ranking by genes' functional categories was in general concordant among different-biovar strains; iii) the median of the half-life time (t1/2) values of transcripts were 15-17 min, indicating that the degree of transcripts' stability seems to correlate with the bacterial intracellular life-style, as these values are considerably higher than the ones observed in other studies for facultative intracellular and free-living bacteria; iv) transcript decay rates were highly heterogeneous within each C...
July 2017: Heliyon
https://www.readbyqxmd.com/read/28792938/m-6-a-mrna-methylation-controls-t-cell-homeostasis-by-targeting-the-il-7-stat5-socs-pathways
#18
Hua-Bing Li, Jiyu Tong, Shu Zhu, Pedro J Batista, Erin E Duffy, Jun Zhao, Will Bailis, Guangchao Cao, Lina Kroehling, Yuanyuan Chen, Geng Wang, James P Broughton, Y Grace Chen, Yuval Kluger, Matthew D Simon, Howard Y Chang, Zhinan Yin, Richard A Flavell
N(6)-methyladenosine (m(6)A) is the most common and abundant messenger RNA modification, modulated by 'writers', 'erasers' and 'readers' of this mark. In vitro data have shown that m(6)A influences all fundamental aspects of mRNA metabolism, mainly mRNA stability, to determine stem cell fates. However, its in vivo physiological function in mammals and adult mammalian cells is still unknown. Here we show that the deletion of m(6)A 'writer' protein METTL3 in mouse T cells disrupts T cell homeostasis and differentiation...
August 9, 2017: Nature
https://www.readbyqxmd.com/read/28783563/stimulation-of-rna-polymerase-ii-ubiquitination-and-degradation-by-yeast-mrna-3-end-processing-factors-is-a-conserved-dna-damage-response-in-eukaryotes
#19
Jason N Kuehner, James W Kaufman, Claire Moore
The quality and retrieval of genetic information is imperative to the survival and reproduction of all living cells. Ultraviolet (UV) light induces lesions that obstruct DNA access during transcription, replication, and repair. Failure to remove UV-induced lesions can abrogate gene expression and cell division, resulting in permanent DNA mutations. To defend against UV damage, cells utilize transcription-coupled nucleotide excision repair (TC-NER) to quickly target lesions within active genes. In cases of long-term genotoxic stress, a slower alternative pathway promotes degradation of RNA Polymerase II (Pol II) to allow for global genomic nucleotide excision repair (GG-NER)...
July 23, 2017: DNA Repair
https://www.readbyqxmd.com/read/28783105/viral-ubiquitin-ligase-stimulates-selective-host-microrna-expression-by-targeting-zeb-transcriptional-repressors
#20
Gabriel Lutz, Igor Jurak, Eui Tae Kim, Ju Youn Kim, Michael Hackenberg, Andrew Leader, Michelle L Stoller, Donna M Fekete, Matthew D Weitzman, Donald M Coen, Angus C Wilson
Infection with herpes simplex virus-1 (HSV-1) brings numerous changes in cellular gene expression. Levels of most host mRNAs are reduced, limiting synthesis of host proteins, especially those involved in antiviral defenses. The impact of HSV-1 on host microRNAs (miRNAs), an extensive network of short non-coding RNAs that regulate mRNA stability/translation, remains largely unexplored. Here we show that transcription of the miR-183 cluster (miR-183, miR-96, and miR-182) is selectively induced by HSV-1 during productive infection of primary fibroblasts and neurons...
August 7, 2017: Viruses
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