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https://www.readbyqxmd.com/read/28100786/inositol-depletion-induced-by-acute-treatment-of-the-bipolar-disorder-drug-valproate-increases-levels-of-phytosphingosine
#1
Shyamalagauri Jadhav, Sarah Russo, L Ashley Cowart, Miriam L Greenberg
Bipolar disorder (BD) is a severe psychiatric illness affecting ~2% of the world population. Valproate (VPA) and lithium, though widely used for the treatment of BD, are not universally effective. These drugs have been shown to cause inositol depletion, but translating this observation to a specific therapeutic mechanism has been difficult, hampering the development of more effective therapies. We have shown previously in yeast that chronic VPA treatment induces the unfolded protein response due to increasing ceramide levels...
January 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28098260/hepatitis-b-virus-x-protein-is-capable-of-down-regulating-protein-level-of-host-antiviral-protein-apobec3g
#2
Ruidong Chen, Xue Zhao, Yongxiang Wang, Youhua Xie, Jing Liu
The apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC) family proteins bind RNA and single-stranded DNA, and create C-to-U base modifications through cytidine deaminase activity. APOBEC3G restricts human immunodeficiency virus 1 (HIV-1) infection by creating hypermutations in proviral DNA, while HIV-1-encoded vif protein antagonizes such restriction by targeting APOBEC3G for degradation. APOBEC3G also inhibits hepatitis B virus (HBV): APOBEC3G co-expression inhibits HBV replication and evidences exist indicating APOBEC3G-mediated HBV hypermutations in patients...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28067465/cholestyramine-alters%C3%A2-bile-acid%C3%A2-amounts-and-the-expression-of-cholesterol-related-genes-in-rabbit-intestinal-and-hepatic-tissues
#3
Dong Ni Qiu, Quan Shang, Da Yu Sun, Wei Qun Ding, Zhong Guang Luo, Jian Chen, Wei Ru Jiang, Jian Ping Huang, Xiao Yun Jiang
OBJECTIVE: Cholestyramine, as a bile acid sequestering exchange resin, has been wildly used to treat hypercholesterolemia. The aim of this study was to explore how cholestyramine regulated serum cholesterol amounts and bile acid levels in animal models. METHODS: The New Zealand White rabbits were randomly assigned to the control (given distilled water) and cholestyramine (CHO)-treated (given cholestyramine 1 g/kg/day for 2 weeks) groups. To assess bile acid pool size, bile fistulas were generated in five rabbits in each group...
January 9, 2017: Journal of Digestive Diseases
https://www.readbyqxmd.com/read/28064320/-interactions-of-the-trex-2-complex-with-mrnp-particle-of-%C3%AE-tubulin-56d-gene
#4
V V Popova, A A Glukhova, S G Georgieva, G P Georgiev, D V Kopytova
mRNA transport from the nucleus to the cytoplasm is an essential step of eukaryotic gene expression. A pre-mRNA molecule undergoes modification, such as 5'-capping, splicing, and 3'-end processing, in the nucleus. The molecule being modified interacts with a large number of proteins and, thus, mRNP particles are formed. The binding of factors involved in nuclear export also occurs during transcription and mRNA processing. We have shown that the functioning of TREX-2, an mRNA export complex, is restricted to the nucleus...
November 2016: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28059701/structural-and-biochemical-analyses-of-the-dead-box-atpase-sub2-in-association-with-tho-or-yra1
#5
Yi Ren, Philip Schmiege, Günter Blobel
mRNA is cotranscrptionally processed and packaged into messenger ribonucleoprotein particles (mRNPs) in the nucleus. Prior to export through the nuclear pore, mRNPs undergo several obligatory remodeling reactions. In yeast, one of these reactions involves loading of the mRNA-binding protein Yra1 by the DEAD-box ATPase Sub2 as assisted by the hetero-pentameric THO complex. To obtain molecular insights into reaction mechanisms, we determined crystal structures of two relevant complexes: a THO hetero-pentamer bound to Sub2 at 6...
January 6, 2017: ELife
https://www.readbyqxmd.com/read/28053097/subcellular-localization-of-hiv-1-gag-pol-mrnas-regulates-sites-of-virion-assembly
#6
Jordan T Becker, Nathan M Sherer
: HIV-1 full-length, unspliced RNAs serve dual roles in the cytoplasm as mRNAs encoding the Gag and Gag-Pol capsid proteins as well as genomic RNAs (gRNAs) packaged by Gag into virions undergoing assembly at the plasma membrane (PM). Because Gag is sufficient to drive assembly of virus-like particles even in the absence of gRNA binding, whether viral RNA trafficking plays an active role in the native assembly pathway is unknown. In this study we tested the effects of modulating the cytoplasmic abundance or distribution of full-length viral RNAs on Gag trafficking and assembly in the context of single cells...
January 4, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28052353/temporal-and-spatial-regulation-of-mrna-export-single-particle-rna-imaging-provides-new-tools-and-insights
#7
Stephanie Heinrich, Carina Patrizia Derrer, Azra Lari, Karsten Weis, Ben Montpetit
The transport of messenger RNAs (mRNAs) from the nucleus to cytoplasm is an essential step in the gene expression program of all eukaryotes. Recent technological advances in the areas of RNA-labeling, microscopy, and sequencing are leading to novel insights about mRNA biogenesis and export. This includes quantitative single molecule imaging (SMI) of RNA molecules in live cells, which is providing knowledge of the spatial and temporal dynamics of the export process. As this information becomes available, it leads to new questions, the reinterpretation of previous findings, and revised models of mRNA export...
January 4, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28039456/microrna-1908-5p-contributes-to-the-oncogenic-function-of-the-splicing-factor-srsf3
#8
Hye Ree Kim, Chang Hoon Shin, Hong Lee, Kyung Hee Choi, Do-Hyun Nam, Takbum Ohn, Hyeon Ho Kim
Serine/arginine (SR)-rich proteins that contain RS domains and SR repeats have diverse cellular functions including transcription, polyadenylation, translation, and RNA export. The splicing factor SRSF3, also termed SRp20, is the smallest member of the SR protein family and is a known proto-oncogene. Although it is implicated in the malignant phenotypes of various cancer cells, the molecular mechanism underlying SRSF3-mediated cancer progression is still obscure. We investigated here the oncogenic functions of SRSF3 in osteosarcoma U2OS cells...
December 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/28036031/drug-transporter-expression-and-activity-in-human-hepatoma-huh-7-cells
#9
Elodie Jouan, Marc Le Vée, Claire Denizot, Yannick Parmentier, Olivier Fardel
Human hepatoma cells may represent a valuable alternative to the use of human hepatocytes for studying hepatic drug transporters, which is now a regulatory issue during drug development. In the present work, we have characterized hepatic drug transporter expression, activity and regulation in human hepatoma HuH-7 cells, in order to determine the potential relevance of these cells for drug transport assays. HuH-7 cells displayed notable multidrug resistance-associated protein (MRP) activity, presumed to reflect expression of various hepatic MRPs, including MRP2...
December 28, 2016: Pharmaceutics
https://www.readbyqxmd.com/read/28035044/a-role-for-gle1-a-regulator-of-dead-box-rna-helicases-at-centrosomes-and-basal-bodies
#10
Li-En Jao, Abdalla Akef, Susan R Wente
Control of organellar assembly and function is critical to eukaryotic homeostasis and survival. Gle1 is a highly conserved regulator of RNA-dependent DEAD-box ATPase proteins, with critical roles in both mRNA export and translation. In addition to its well-defined interaction with nuclear pore complexes, here we find that Gle1 is enriched at the centrosome and basal body. Gle1 assembles into the toroid-shaped pericentriolar material around the mother centriole. Reduced Gle1 levels are correlated with decreased pericentrin localization at the centrosome and microtubule organization defects...
January 1, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28028052/an-rna-binding-atypical-tropomyosin-recruits-kinesin-1-dynamically-to-oskar-mrnps
#11
Imre Gáspár, Vasiliy Sysoev, Artem Komissarov, Anne Ephrussi
Localization and local translation of oskar mRNA at the posterior pole of the Drosophila oocyte directs abdominal patterning and germline formation in the embryo. The process requires recruitment and precise regulation of motor proteins to form transport-competent mRNPs. We show that the posterior-targeting kinesin-1 is loaded upon nuclear export of oskar mRNPs, prior to their dynein-dependent transport from the nurse cells into the oocyte. We demonstrate that kinesin-1 recruitment requires the DmTropomyosin1-I/C isoform, an atypical RNA-binding tropomyosin that binds directly to dimerizing oskar 3'UTRs...
December 27, 2016: EMBO Journal
https://www.readbyqxmd.com/read/28008720/the-exon-junction-complex-a-lifelong-guardian-of-mrna-fate
#12
REVIEW
Lauren A Woodward, Justin W Mabin, Pooja Gangras, Guramrit Singh
During messenger RNA (mRNA) biogenesis and processing in the nucleus, many proteins are imprinted on mRNAs assembling them into messenger ribonucleoproteins (mRNPs). Some of these proteins remain stably bound within mRNPs and have a long-lasting impact on their fate. One of the best-studied examples is the exon junction complex (EJC), a multiprotein complex deposited primarily 24 nucleotides upstream of exon-exon junctions as a consequence of pre-mRNA splicing. The EJC maintains a stable, sequence-independent, hold on the mRNA until its removal during translation in the cytoplasm...
December 23, 2016: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/28004241/the-arabidopsis-tho-trex-component-tex1-functionally-interacts-with-mos11-and-modulates-mrna-export-and-alternative-splicing-events
#13
Brian B Sørensen, Hans F Ehrnsberger, Silvia Esposito, Alexander Pfab, Astrid Bruckmann, Judith Hauptmann, Gunter Meister, Rainer Merkl, Thomas Schubert, Gernot Längst, Michael Melzer, Marion Grasser, Klaus D Grasser
We identify proteins that associate with the THO core complex, and show that the TEX1 and MOS11 components functionally interact, affecting mRNA export and splicing as well as plant development. TREX (TRanscription-EXport) is a multiprotein complex that plays a central role in the coordination of synthesis, processing and nuclear export of mRNAs. Using targeted proteomics, we identified proteins that associate with the THO core complex of Arabidopsis TREX. In addition to the RNA helicase UAP56 and the mRNA export factors ALY2-4 and MOS11 we detected interactions with the mRNA export complex TREX-2 and multiple spliceosomal components...
December 21, 2016: Plant Molecular Biology
https://www.readbyqxmd.com/read/27988213/down-regulation-of-abcg2-a-urate-exporter-by-parathyroid-hormone-enhances-urate-accumulation-in-secondary-hyperparathyroidism
#14
Ryusei Sugimoto, Hiroshi Watanabe, Komei Ikegami, Yuki Enoki, Tadashi Imafuku, Yoshiaki Sakaguchi, Michiya Murata, Kento Nishida, Shigeyuki Miyamura, Yu Ishima, Motoko Tanaka, Kazutaka Matsushita, Hirotaka Komaba, Masafumi Fukagawa, Masaki Otagiri, Toru Maruyama
Hyperuricemia occurs with increasing frequency among patients with hyperparathyroidism. However, the molecular mechanism by which the serum parathyroid hormone (PTH) affects serum urate levels remains unknown. This was studied in uremic rats with secondary hyperparathyroidism where serum urate levels were found to be increased and urate excretion in the intestine and kidney decreased, presumably due to down-regulation of the expression of the urate exporter ABCG2 in intestinal and renal epithelial membranes...
December 14, 2016: Kidney International
https://www.readbyqxmd.com/read/27967316/adipogenic-impairment-of-adipose-tissue-derived-mesenchymal-stem-cells-in-subjects-with-metabolic-syndrome-possible-protective-role-of-fgf2
#15
Wilfredo Oliva-Olivera, Leticia Coín-Aragüez, Said Lhamyani, Mercedes Clemente-Postigo, Juan Alcaide Torres, Maria Rosa Bernal-López, Rajaa El Bekay, Francisco José Tinahones
CONTEXT: The decreased expansion capacity of adipose tissue plays a crucial role in the onset of disorders associated with metabolic syndrome. Objetive: The aim of this study was to examine the state of adipose tissue-derived mesenchymal stem cells (ASCs) from obese subjects with different metabolic profiles. DESIGN: This was a 2-year study to enroll subjects who underwent bariatric surgery or cholecystectomy. SETTING: University Hospital Patients and Intervention: Patients who underwent either bariatric surgery (20 morbidly obese) or cholecystectomy (40 subjects) participated in the study...
December 14, 2016: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27951587/mrna-quality-control-is-bypassed-for-immediate-export-of-stress-responsive-transcripts
#16
Gesa Zander, Alexandra Hackmann, Lysann Bender, Daniel Becker, Thomas Lingner, Gabriela Salinas, Heike Krebber
Cells grow well only in a narrow range of physiological conditions. Surviving extreme conditions requires the instantaneous expression of chaperones that help to overcome stressful situations. To ensure the preferential synthesis of these heat-shock proteins, cells inhibit transcription, pre-mRNA processing and nuclear export of non-heat-shock transcripts, while stress-specific mRNAs are exclusively exported and translated. How cells manage the selective retention of regular transcripts and the simultaneous rapid export of heat-shock mRNAs is largely unknown...
December 12, 2016: Nature
https://www.readbyqxmd.com/read/27940554/rna-helicase-ddx19-stabilizes-ribosomal-elongation-and-termination-complexes
#17
Tatiana Mikhailova, Ekaterina Shuvalova, Alexander Ivanov, Denis Susorov, Alexey Shuvalov, Peter M Kolosov, Elena Alkalaeva
The human DEAD-box RNA-helicase DDX19 functions in mRNA export through the nuclear pore complex. The yeast homolog of this protein, Dbp5, has been reported to participate in translation termination. Using a reconstituted mammalian in vitro translation system, we show that the human protein DDX19 is also important for translation termination. It is associated with the fraction of translating ribosomes. We show that DDX19 interacts with pre-termination complexes (preTCs) in a nucleotide-dependent manner. Furthermore, DDX19 increases the efficiency of termination complex (TC) formation and the peptide release in the presence of eukaryotic release factors...
December 9, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27934633/c-myc-co-ordinates-mrna-cap-methylation-and-ribosomal-rna-production
#18
Sianadh Dunn, Olivia Lombardi, Victoria H Cowling
The mRNA cap is a structure added to RNA pol II transcripts in eukaryotes, which recruits factors involved in RNA processing, nuclear export and translation initiation.  RNMT-RAM, the mRNA cap methyltransferase complex, completes the basic functional mRNA cap structure, cap 0, by methylating the cap guanosine.  Here we report that RNMT-RAM co-ordinates mRNA processing with ribosome production.  Suppression of RNMT-RAM reduces synthesis of the 45S ribosomal RNA (rRNA) precursor.  RNMT-RAM is required for c-Myc expression, a major regulator of RNA pol I, which synthesises 45S rRNA...
December 1, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27921095/journey-from-the-center-of-the-cell-the-intra-and-intercellular-transport-of-mrna
#19
REVIEW
Anna Kasprowicz-Maluśki, Wojciech Kwiatkowski, Alicja Starosta, Przemysław Wojtaszek
Transport and localized translation of mRNA is crucial for the proper spatiotemporal organization of proteins within cells. Distribution of RNAs to subcellular domains has recently emerged as a major mechanism for establishing functionally distinct compartments and structures in the cells. There is an emerging evidence that active transport of mRNA involves cytoskeleton and membrane trafficking pathways in fungi, plants and animals, suggesting that it is a common phenomenon among eukaryotes. The important highlights are that the RNA-binding proteins recognize the cargo mRNA and that RNPs are actively transported on the cytoskeletal tracks or co-transported with membranous compartments, such as the endoplasmic reticulum and endosomes...
2016: Acta Biochimica Polonica
https://www.readbyqxmd.com/read/27903772/diverse-activities-of-viral-cis-acting-rna-regulatory-elements-revealed-using-multi-color-long-term-single-cell-imaging
#20
Ginger M Pocock, Laraine L Zimdars, Ming Yuan, Kevin W Eliceiri, Paul Ahlquist, Nathan M Sherer
Cis-acting RNA structural elements govern crucial aspects of viral gene expression. How these structures and other post-transcriptional signals affect RNA trafficking and translation in the context of single cells is poorly understood. Herein we describe a multi-color, long-term (>24 h) imaging strategy for measuring integrated aspects of viral RNA regulatory control in individual cells. We apply this strategy to demonstrate differential mRNA trafficking behaviors governed by RNA elements derived from three retroviruses (HIV-1, murine leukemia virus, and Mason-Pfizer monkey virus), two hepadnaviruses (hepatitis B virus and woodchuck hepatitis virus) and an intron-retaining transcript encoded by the cellular NXF1 gene...
November 30, 2016: Molecular Biology of the Cell
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