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https://www.readbyqxmd.com/read/28516119/affinity-pulldown-of-biotinylated-rna-for-detection-of-protein-rna-complexes
#1
Amaresh C Panda, Jennifer L Martindale, Myriam Gorospe
RNA-binding proteins (RBPs) have recently emerged as crucial players in the regulation of gene expression. The interactions of RBPs with target mRNAs control the levels of gene products by altering different regulatory steps, including pre-mRNA splicing and maturation, nuclear mRNA export, and mRNA stability and translation (Glisovic et al., 2008). There are several methodologies available today to identify RNAs bound to specific RBPs; some detect only recombinant molecules in vitro, others detect recombinant and endogenous molecules, while others detect only endogenous molecules...
December 20, 2016: Bio-protocol
https://www.readbyqxmd.com/read/28515301/the-influenza-a-virus-ns1-protein-promotes-efficient-nuclear-export-of-unspliced-viral-m1-mrna
#2
Carina F Pereira, Eliot K C Read, Helen M Wise, Maria J Amorim, Paul Digard
Influenza A virus mRNAs are transcribed by the viral RNA-dependent RNA polymerase in the cell nucleus before being exported to the cytoplasm for translation. Segment 7 produces two major transcripts: an unspliced mRNA that encodes the M1 matrix protein and a spliced transcript that encodes the M2 ion channel. Export of both mRNAs is dependent on the cellular NXF1/TAP pathway but it is unclear how they are recruited to the export machinery or how the intron-containing but unspliced M1 mRNA bypasses the normal quality control checkpoints...
May 17, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28507548/iron-and-hepcidin-independent-downregulation-of-the-iron-exporter-ferroportin-in-macrophages-during-salmonella-infection
#3
Alexandra Willemetz, Sean Beatty, Etienne Richer, Aude Rubio, Anne Auriac, Ruth J Milkereit, Olivier Thibaudeau, Sophie Vaulont, Danielle Malo, François Canonne-Hergaux
Retention of iron in tissue macrophages via upregulation of hepcidin (HAMP) and downregulation of the iron exporter ferroportin (FPN) is thought to participate in the establishment of anemia of inflammation after infection. However, an upregulation of FPN has been proposed to limit macrophages iron access to intracellular pathogens. Therefore, we studied the iron homeostasis and in particular the regulation of FPN after infection with Salmonella enterica serovar Typhimurium in mice presenting tissue macrophages with high iron (AcB61), basal iron (A/J and wild-type mice), or low iron (Hamp knock out, Hamp(-/-)) levels...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28505368/farnesoid-x-receptor-protects-against-low-dose-carbon-tetrachloride-induced-liver-injury-through-the-taurocholate-jnk-pathway
#4
Shogo Takahashi, Naoki Tanaka, Srujana Golla, Tatsuki Fukami, Kristopher W Krausz, Marianne A Polunas, Blair C Weig, Yusuke Masuo, Cen Xie, Changtao Jiang, Frank J Gonzalez
Hepatotoxicity is of major concern for humans exposed to industrial chemicals and drugs. Disruption of farnesoid X receptor (FXR), a master regulator of bile acid (BA) metabolism, enhanced the sensitivity to liver injury in mice after toxicant exposure, but the precise mechanism remains unclear. In this study, the interconnection between BA metabolism, FXR, and chemically-induced hepatotoxicity was investigated using metabolomics, Fxr-null mice and hepatocytes, and adenovirus. A single low-dose intraperitoneal injection of carbon tetrachloride (CCl4), an inducer of acute hepatitis in mice, resulted in more severe hepatocyte damage and higher induction of pro-inflammatory mediators, such as chemokine (C-C motif) ligand 2 (Ccl2), in Fxr-null mice...
May 15, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28501703/xanthohumol-a-hop-derived-prenylated-flavonoid-promotes-macrophage-reverse-cholesterol-transport
#5
Hiroshi Hirata, Harumi Uto-Kondo, Masatsune Ogura, Makoto Ayaori, Kazusa Shiotani, Ami Ota, Youichi Tsuchiya, Katsunori Ikewaki
Xanthohumol, a prominent prenyl flavonoid from the hop plant (Humulus lupulus L.), is suggested to be antiatherogenic since it reportedly increases high-density lipoprotein (HDL) cholesterol levels. It is not clear whether xanthohumol promotes reverse cholesterol transport (RCT), the most important antiatherogenic property of HDL; therefore, we investigated the effects of xanthohumol on macrophage-to-feces RCT using a hamster model as a CETP-expressing species. In vivo RCT experiments showed that xanthohumol significantly increased fecal appearance of the tracer derived from intraperitoneally injected [(3)H]-cholesterol-labeled macrophages...
April 22, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28498392/the-flightless-i-protein-interacts-with-rna-binding-proteins-and-is-involved-in-the-genome-wide-mrna-post-transcriptional-regulation-in-lung-carcinoma-cells
#6
Cuihua Wang, Kezhi Chen, Shengyou Liao, Wei Gu, Xinlei Lian, Jing Zhang, Xuejuan Gao, Xiaohui Liu, Tong Wang, Qing-Yu He, Gong Zhang, Langxia Liu
The flightless I protein (FLII) belongs to the gelsolin family. Its function has been associated with actin remodeling, embryonic development, wound repair, and more recently with cancer. The structure of FLII is characterized by the N-terminal leucine-rich repeats (LRR) and C-terminal gesolin related repeated units that are both protein-protein inter-action domains, suggesting that FLII may exert its function by interaction with other proteins. Therefore, systematic study of protein interactions of FLII in cells is important for the understanding of FLII functions...
May 11, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28483564/the-influence-of-nuclear-compartmentalisation-on-stochastic-dynamics-of-self-repressing-gene-expression
#7
Marc Sturrock, Shiyu Li, Vahid Shahrezaei
Gene expression is an inherently noisy process. This noise is generally thought to be deleterious as precise internal regulation of biochemical reactions is essential for cell growth and survival. Self-repression of gene expression, which is the simplest form of a negative feedback loop, is commonly believed to be employed by cellular systems to decrease the stochastic fluctuations in gene expression. When there is some delay in autoregulation, it is also believed that this system can generate oscillations...
May 5, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28472378/efflux-transporters-regulate-arsenite-induced-genotoxicity-in-double-negative-and-double-positive-t-cells
#8
Huan Xu, Sebastian Medina, Fredine T Lauer, Christelle Douillet, Ke Jian Liu, Laurie G Hudson, Miroslav Stýblo, Lauren M Aleksunes, Scott W Burchiel
Arsenite (As+3) exposure is known to cause immunotoxicity in human and animal models. Our previous studies demonstrated that As+3 at 50 to 500 nM concentrations induced both genotoxicity and non-genotoxicity in mouse thymus cells. Developing T cells at CD4-CD8- double negative (DN) stage, the first stage after early T cells are transported from bone marrow to thymus, were found to be more sensitive to As+3 toxicity than the T cells at CD4+CD8+ double positive (DP) stage in vitro. Induction of Mdr1 (Abcb1) and Mrp1 (Abcc1), two multidrug resistance transporters and exporters of As+3, was associated with the reversal of As+3-induced double strand breaks and DNA damage...
April 29, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28463551/comparative-interactomics-provides-evidence-for-functional-specialization-of-the-nuclear-pore-complex
#9
Samson O Obado, Mark C Field, Michael P Rout
The core architecture of the eukaryotic cell was established well over one billion years ago, and is largely retained in all extant lineages. However, eukaryotic cells also possess lineage-specific features, frequently keyed to specific functional requirements. One quintessential core eukaryotic structure is the nuclear pore complex (NPC), responsible for regulating exchange of macromolecules between the nucleus and cytoplasm as well as acting as a nuclear organizational hub. NPC architecture has been best documented in one eukaryotic supergroup, the Opisthokonts (e...
May 2, 2017: Nucleus
https://www.readbyqxmd.com/read/28460002/proteomic-analysis-of-polyribosomes-identifies-splicing-factors-as-potential-regulators-of-translation-during-mitosis
#10
Ranen Aviner, Sarah Hofmann, Tamar Elman, Anjana Shenoy, Tamar Geiger, Ran Elkon, Marcelo Ehrlich, Orna Elroy-Stein
Precise regulation of mRNA translation is critical for proper cell division, but little is known about the factors that mediate it. To identify mRNA-binding proteins that regulate translation during mitosis, we analyzed the composition of polysomes from interphase and mitotic cells using unbiased quantitative mass-spectrometry (LC-MS/MS). We found that mitotic polysomes are enriched with a subset of proteins involved in RNA processing, including alternative splicing and RNA export. To demonstrate that these may indeed be regulators of translation, we focused on heterogeneous nuclear ribonucleoprotein C (hnRNP C) as a test case and confirmed that it is recruited to elongating ribosomes during mitosis...
April 29, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28456604/herpesviruses-hijack-host-exosomes-for-viral-pathogenesis
#11
REVIEW
Sara Sadeghipour, Rommel A Mathias
Herpesviruses are remarkable pathogens possessing elaborate mechanisms to seize various host cellular components for immune evasion, replication, and virion egress. As viruses are dependent upon their hosts, investigating this intricate interplay has revealed that the exosome pathway is utilised by alpha (Herpes Simplex Virus 1), beta (Human Cytomegalovirus, and Human Herpesvirus 6) and gamma (Epstein-Barr Virus, and Kaposi Sarcoma-associated Herpesvirus) herpesviruses. Virions and exosomes share similar properties and functions...
April 26, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28453393/cleavage-and-polyadenylation-ending-the-message-expands-gene-regulation
#12
Jonathan Neve, Radhika Patel, Zhiqiao Wang, Alastair Louey, André Martin Furger
Cleavage and polyadenylation (pA) is a fundamental step that is required for the maturation of primary protein encoding transcripts into functional mRNAs that can be exported from the nucleus and translated in the cytoplasm. 3'end processing is dependent on the assembly of a multiprotein processing complex on the pA signals that reside in the pre-mRNAs. Most eukaryotic genes have multiple pA signals, resulting in alternative cleavage and polyadenylation (APA), a widespread phenomenon that is important to establish cell state and cell type specific transcriptomes...
April 28, 2017: RNA Biology
https://www.readbyqxmd.com/read/28450399/the-crystal-structure-of-mammalian-inositol-1-3-4-5-6-pentakisphosphate-2-kinase-reveals-a-new-zinc-binding-site-and-key-features-for-protein-function
#13
Elsa Franco-Echevarria, Julia Sanz-Aparicio, Charles A Brearley, Juana M Gonzalez-Rubio, Beatriz Gonzalez
Inositol 1,3,4,5,6-pentakisphosphate 2-kinases (IP5 2-Ks) comprise a family of enzymes in charge of synthesizing inositol hexakisphosphate (IP6) in eukaryotic cells. This protein and its product IP6 present many roles in cells, participating in mRNA export, embryonic development, and apoptosis. We reported previously that the full-length IP5 2-K from Arabidopsis thaliana (At) is a zinc metallo-enzyme including two separated lobes (the N and C lobes). We have also shown conformational changes in IP5 2-K and have identified the residues involved in substrate recognition and catalysis...
April 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28440291/identifying-n-6-methyladenosine-sites-using-multi-interval-nucleotide-pair-position-specificity-and-support-vector-machine
#14
Pengwei Xing, Ran Su, Fei Guo, Leyi Wei
N6-methyladenosine (m(6)A) refers to methylation of the adenosine nucleotide acid at the nitrogen-6 position. It plays an important role in a series of biological processes, such as splicing events, mRNA exporting, nascent mRNA synthesis, nuclear translocation and translation process. Numerous experiments have been done to successfully characterize m(6)A sites within sequences since high-resolution mapping of m(6)A sites was established. However, as the explosive growth of genomic sequences, using experimental methods to identify m(6)A sites are time-consuming and expensive...
April 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28436945/adar1-controls-apoptosis-of-stressed-cells-by-inhibiting-staufen1-mediated-mrna-decay
#15
Masayuki Sakurai, Yusuke Shiromoto, Hiromitsu Ota, Chunzi Song, Andrew V Kossenkov, Jayamanna Wickramasinghe, Louise C Showe, Emmanuel Skordalakes, Hsin-Yao Tang, David W Speicher, Kazuko Nishikura
Both p150 and p110 isoforms of ADAR1 convert adenosine to inosine in double-stranded RNA (dsRNA). ADAR1p150 suppresses the dsRNA-sensing mechanism that activates MDA5-MAVS-IFN signaling in the cytoplasm. In contrast, the biological function of the ADAR1p110 isoform, which is usually located in the nucleus, is largely unknown. Here, we show that stress-activated phosphorylation of ADAR1p110 by MKK6-p38-MSK MAP kinases promotes its binding to Exportin-5 and its export from the nucleus. After translocating to the cytoplasm, ADAR1p110 suppresses apoptosis in stressed cells by protecting many antiapoptotic gene transcripts that contain 3'-untranslated-region dsRNA structures primarily comprising inverted Alu repeats...
April 24, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28432334/regulation-of-viral-gene-expression-by-duck-enteritis-virus-ul54
#16
Chaoyue Liu, Anchun Cheng, Mingshu Wang, Shun Chen, Renyong Jia, Dekang Zhu, Mafeng Liu, Kunfeng Sun, Qiao Yang, Ying Wu, Xinxin Zhao, Xiaoyue Chen
Duck enteritis virus (DEV) UL54 is a homologue of human herpes simplex virus-1 (HSV-1) ICP27, which plays essential regulatory roles during infection. Our previous studies indicated that DEV UL54 is an immediate-early protein that can shuttle between the nucleus and the cytoplasm. In the present study, we found that UL54-deleted DEV (DEV-ΔUL54) exhibits growth kinetics, a plaque size and a viral DNA copy number that are significantly different from those of its parent wild-type virus (DEV-LoxP) and the revertant (DEV-ΔUL54 (Revertant))...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28420424/a-novel-lncrna-uc-134-represses-hepatocellular-carcinoma-progression-by-inhibiting-cul4a-mediated-ubiquitination-of-lats1
#17
Wen Ni, Yuqin Zhang, Zetao Zhan, Feng Ye, Yonghao Liang, Jing Huang, Keli Chen, Longhua Chen, Yi Ding
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, and tumor recurrence and metastasis are major factors that contribute to the poor outcome of patients with HCC. Long noncoding RNAs (lncRNAs) are known to regulate different tumorigenic processes, and a growing body of evidence indicates that Hippo kinase signaling is inactivated in many cancers. However, the upstream lncRNA regulators of Hippo kinase signaling in HCC are poorly understood. METHODS: Using a lncRNA microarray, we identified a novel lncRNA, uc...
April 19, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28418038/5-methylcytosine-promotes-mrna-export-nsun2-as-the-methyltransferase-and-alyref-as-an-m-5-c-reader
#18
Xin Yang, Ying Yang, Bao-Fa Sun, Yu-Sheng Chen, Jia-Wei Xu, Wei-Yi Lai, Ang Li, Xing Wang, Devi Prasad Bhattarai, Wen Xiao, Hui-Ying Sun, Qin Zhu, Hai-Li Ma, Samir Adhikari, Min Sun, Ya-Juan Hao, Bing Zhang, Chun-Min Huang, Niu Huang, Gui-Bin Jiang, Yong-Liang Zhao, Hai-Lin Wang, Ying-Pu Sun, Yun-Gui Yang
5-methylcytosine (m(5)C) is a post-transcriptional RNA modification identified in both stable and highly abundant tRNAs and rRNAs, and in mRNAs. However, its regulatory role in mRNA metabolism is still largely unknown. Here, we reveal that m(5)C modification is enriched in CG-rich regions and in regions immediately downstream of translation initiation sites and has conserved, tissue-specific and dynamic features across mammalian transcriptomes. Moreover, m(5)C formation in mRNAs is mainly catalyzed by the RNA methyltransferase NSUN2, and m(5)C is specifically recognized by the mRNA export adaptor ALYREF as shown by in vitro and in vivo studies...
April 18, 2017: Cell Research
https://www.readbyqxmd.com/read/28402257/-dead-box-rna-helicase-3-modulates-nf-%C3%AE%C2%BAb-signal-pathway-by-controlling-the-phosphorylation-of-pp2a-c-subunit
#19
Xin Wang, Rui Wang, Miao Luo, Chen Li, Hua-Xia Wang, Chang-Chao Huan, Yu-Rong Qu, Ying Liao, Xiang Mao
Asp-Glu-Ala-Asp (DEAD)-box RNA helicase 3 (DDX3), an ATP-dependent RNA helicase, is associated with RNA splicing, mRNA export, transcription, translation, and RNA decay. Recent studies revealed that DDX3 participates in innate immune response during virus infection by interacting with TBK1 and regulating the production of IFN-β. In our studies, we demonstrated that DDX3 regulated NF-κB signal pathway. We found that DDX3 knockdown reduced the phosphorylation of p65 and IKK-β and ultimately attenuated the production of inflammatory cytokines induced by poly(I:C) or TNF-α stimulation...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28382373/antagonists-of-the-system-l-neutral-amino-acid-transporter-lat-promote-endothelial-adhesivity-of-human-red-blood-cells
#20
Laura Beth Mann Dosier, Vikram J Premkumar, Hongmei Zhu, Izzet Akosman, Michael F Wempe, Timothy J McMahon
The system L neutral amino acid transporter (LAT; LAT1, LAT2, LAT3, or LAT4) has multiple functions in human biology, including the cellular import of S-nitrosothiols (SNOs), biologically active derivatives of nitric oxide (NO). SNO formation by haemoglobin within red blood cells (RBC) has been studied, but the conduit whereby a SNO leaves the RBC remains unidentified. Here we hypothesised that SNO export by RBCs may also depend on LAT activity, and investigated the role of RBC LAT in modulating SNO-sensitive RBC-endothelial cell (EC) adhesion...
April 6, 2017: Thrombosis and Haemostasis
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