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https://www.readbyqxmd.com/read/29329719/regulatory-potential-of-the-rna-processing-machinery-implications-for-human-disease
#1
REVIEW
Kirstyn T Carey, Vihandha O Wickramasinghe
Splicing and nuclear export of mRNA are critical steps in the gene expression pathway. While RNA processing factors can perform general, essential functions for intron removal and bulk export of mRNA, emerging evidence highlights that the core RNA splicing and export machineries also display regulatory potential. Here, we discuss recent insights into how this regulatory potential can selectively alter gene expression and regulate important biological processes. We also highlight the participation of RNA processing pathways in the cellular response to DNA damage at multiple levels...
January 9, 2018: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/29326041/role-of-the-mrna-export-factor-sus1-in-oxidative-stress-tolerance-in-candida-albicans
#2
Chenpeng Xiao, Qilin Yu, Bing Zhang, Jianrong Li, Dan Zhang, Mingchun Li
In eukaryotes, the nuclear export of mRNAs is essential for gene expression. However, little is known about the role of mRNA nuclear export in the important fungal pathogen, Candida albicans. In this study, we identified C. albicans Sus1, a nucleus-localized protein that is required for mRNA export. Interestingly, the sus1Δ/Δ displayed hyper-sensitivity to extracellular oxidative stress, enhanced ROS accumulation and severe oxidative stress-related cell death. More strikingly, although the mutant exhibited normal activation of the expression of oxidative stress response (OSR) genes, it had attenuated activity of ROS scavenging system, which may be attributed to the defect in OSR mRNA export in this mutant...
January 8, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29246313/assessment-of-the-drug-interaction-potential-of-unconjugated-and-galnac3-conjugated-2-moe-asos
#3
Colby S Shemesh, Rosie Z Yu, Mark S Warren, Michael Liu, Mirza Jahic, Brandon Nichols, Noah Post, Song Lin, Daniel A Norris, Eunju Hurh, Jane Huang, Tanya Watanabe, Scott P Henry, Yanfeng Wang
Antisense oligonucleotides are metabolized by nucleases and drug interactions with small drug molecules at either the cytochrome P450 (CYP) enzyme or transporter levels have not been observed to date. Herein, a comprehensive in vitro assessment of the drug-drug interaction (DDI) potential was carried out with four 2'-O-(2-methoxyethyl)-modified antisense oligonucleotides (2'-MOE-ASOs), including a single triantennary N-acetyl galactosamine (GalNAc3)-conjugated ASO. Several investigations to describe the DDI potential of a 2'-MOE-ASO conjugated to a high-affinity ligand for hepatocyte-specific asialoglycoprotein receptors are explored...
December 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/29243174/prion-propagation-and-inositol-polyphosphates
#4
REVIEW
Reed B Wickner, Herman K Edskes, Evgeny E Bezsonov, Moonil Son, Mathieu Ducatez
The [PSI+] prion is a folded in-register parallel β-sheet amyloid (filamentous polymer) of Sup35p, a subunit of the translation termination factor. Our searches for anti-prion systems led to our finding that certain soluble inositol polyphosphates (IPs) are important for the propagation of the [PSI+] prion. The IPs affect a wide range of processes, including mRNA export, telomere length, phosphate and polyphosphate metabolism, energy regulation, transcription and translation. We found that 5-diphosphoinositol tetra(or penta)kisphosphate or inositol hexakisphosphate could support [PSI+] prion propagation, and 1-diphosphoinositol pentakisphosphate appears to inhibit the process...
December 14, 2017: Current Genetics
https://www.readbyqxmd.com/read/29234671/a-new-role-for-the-nuclear-basket-network
#5
COMMENT
Paola Gallardo, Silvia Salas-Pino, Rafael R Daga
Our view of the nuclear pore complexes (NPCs) as gateways between the nuclear and cytoplasmic compartments has been largely expanded in recent years. NPCs have now demonstrated roles in genome regulation and maintenance from single cells to multicellular organisms. Both NPC proteins as well as components of the NPC basket act as dynamic scaffolds for silencing factors, and chromatin and cell cycle regulators. Components of the NPC basket also couple mRNA production and export, and prevent the exit of unprocessed mRNAs from the nucleus...
November 27, 2017: Microbial Cell
https://www.readbyqxmd.com/read/29229136/the-gut-liver-axis-impact-of-a-mouse-model-of-small-bowel-bacterial-overgrowth
#6
Qingqing Wang, Bin Wang, Vijay Saxena, Lili Miles, Josh Tiao, Joel E Mortensen, Jaimie D Nathan
BACKGROUND: The mechanisms by which intestinal bacteria impact liver diseases remain poorly understood. The aim of this study was to develop a mouse model of small-bowel bacterial overgrowth and to determine its impact on hepatobiliary injury. MATERIALS AND METHODS: A jejunal self-filling blind loop (SFBL) was created in C57BL/6 mice. Three weeks after surgery, the mice were euthanized, and bacterial cultures of luminal content of the loop and extraintestinal tissues were performed...
January 2018: Journal of Surgical Research
https://www.readbyqxmd.com/read/29228114/effects-of-exportin-1-on-nuclear-transport-and-meiotic-resumption-in-porcine-full-grown-and-growing-oocytes
#7
Asuka Onuma, Yoshie A Fujioka, Wataru Fujii, Koji Sugiura, Kunihiko Naito
Exportin 1 (XPO1) is a nuclear transport receptor involved in the nuclear export of majority proteins in somatic cells. In mammalian oocytes, however, only the presence of XPO1 has been reported at mRNA and protein levels, and the definitive functions of XPO1 and its effects on the meiotic maturation of oocytes have never been directly examined. In the present study, the expression state and the nuclear-export function of porcine XPO1 were analyzed in porcine oocytes. In addition, we investigated the effects of the overexpression and inhibition of XPO1 on meiotic regulation in full-grown and growing oocytes by mRNA injection and inhibitor treatment...
December 8, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/29225167/adenovirus-infection-induces-hur-relocalization-to-facilitate-virus-replication
#8
Jumond P Jehung, Tetsuya Kitamura, Aya Yanagawa-Matsuda, Takeshi Kuroshima, Alam Towfik, Motoaki Yasuda, Hidehiko Sano, Yoshimasa Kitagawa, Kazuyuki Minowa, Masanobu Shindoh, Fumihiro Higashino
HuR is an RNA-binding protein of the embryonic lethal abnormal vision (ELAV) family, which binds to the AU-rich element (ARE) in the 3'-untranslated region (UTR) of certain mRNAs and is involved in the nucleo-cytoplasmic export and stabilization of ARE-mRNAs. The cytoplasmic relocalization of ARE-mRNAs with several proteins such as HuR and pp32 increases in cells transformed by the adenovirus oncogene product E4orf6. Additionally, these ARE-mRNAs were stabilized and acquired the potential to transform cells...
December 7, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29225038/cell-cycle-control-by-nuclear-sequestration-of-cdc20-and-cdh1-mrna-in-plant-stem-cells
#9
Weibing Yang, Raymond Wightman, Elliot M Meyerowitz
In eukaryotes, most RNA molecules are exported into the cytoplasm after transcription. Long noncoding RNAs (lncRNAs) reside and function primarily inside the nucleus, but nuclear localization of mRNAs has been considered rare in both animals and plants. Here we show that Arabidopsis anaphase-promoting complex/cyclosome (APC/C) coactivator genes CDC20 and CCS52B (CDH1 ortholog) are co-expressed with their target cyclin B genes (CYCBs) during mitosis. CYCB transcripts can be exported and translated; however, CDC20 and CCS52B mRNAs are confined to the nucleus at prophase, and the cognate proteins are not translated until the redistribution of the mRNAs to the cytoplasm after nuclear envelope breakdown (NEBD) at prometaphase...
December 5, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29215867/direct-substrate-identification-with-an-analog-sensitive-as-viral-cyclin-dependent-kinase-v-cdk
#10
Angie C Umaña, Satoko Iwahori, Robert F Kalejta
Viral cyclin-dependent kinases (v-Cdks) functionally emulate their cellular Cdk counterparts. Such viral mimicry is an established phenomenon that we extend here through chemical genetics. Kinases contain gatekeeper residues that limit the size of molecules that can be accommodated within the enzyme active site. Mutating gatekeeper residues to smaller amino acids allows larger molecules access to the active site. Such mutants can utilize bio-orthoganol ATPs for phosphate transfer and are inhibited by compounds ineffective against the wild type protein, and thus are referred to as analog-sensitive (AS) kinases...
December 7, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/29214018/transcriptional-changes-in-mesenteric-and-subcutaneous-adipose-tissue-from-holstein-cows-in-response-to-plane-of-dietary-energy
#11
S J Moisá, P Ji, J K Drackley, S L Rodriguez-Zas, J J Loor
Background: Dairy cows can readily overconsume dietary energy during most of the prepartum period, often leading to higher prepartal concentrations of insulin and glucose and excessive body fat deposition. The end result of these physiologic changes is greater adipose tissue lipolysis post-partum coupled with excessive hepatic lipid accumulation and compromised health. Although transcriptional regulation of the adipose response to energy availability is well established in non-ruminants, such regulation in cow adipose tissue depots remains poorly characterized...
2017: Journal of Animal Science and Biotechnology
https://www.readbyqxmd.com/read/29212662/sharing-the-load-mex67-mtr2-cofunctions-with-los1-in-primary-trna-nuclear-export
#12
Kunal Chatterjee, Shubhra Majumder, Yao Wan, Vijay Shah, Jingyan Wu, Hsiao-Yun Huang, Anita K Hopper
Eukaryotic transfer RNAs (tRNAs) are exported from the nucleus, their site of synthesis, to the cytoplasm, their site of function for protein synthesis. The evolutionarily conserved β-importin family member Los1 (Exportin-t) has been the only exporter known to execute nuclear export of newly transcribed intron-containing pre-tRNAs. Interestingly, LOS1 is unessential in all tested organisms. As tRNA nuclear export is essential, we previously interrogated the budding yeast proteome to identify candidates that function in tRNA nuclear export...
December 6, 2017: Genes & Development
https://www.readbyqxmd.com/read/29204148/insights-into-the-mechanisms-underlying-boron-homeostasis-in-plants
#13
REVIEW
Akira Yoshinari, Junpei Takano
Boron is an essential element for plants but is toxic in excess. Therefore, plants must adapt to both limiting and excess boron conditions for normal growth. Boron transport in plants is primarily based on three transport mechanisms across the plasma membrane: passive diffusion of boric acid, facilitated diffusion of boric acid via channels, and export of borate anion via transporters. Under boron -limiting conditions, boric acid channels and borate exporters function in the uptake and translocation of boron to support growth of various plant species...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29198193/regulation-of-hepatic-lipid-deposition-by-phospholipid-in-large-yellow-croaker
#14
Zuonan Cai, Kangsen Mai, Qinghui Ai
Dietary phospholipid (PL) supplementation has been shown to reduce lipid accumulation in the tissues of farmed fish; however, the mechanisms underlying this effect are largely unknown. Thus, the present study was conducted to evaluate the potential impacts of PL on hepatic lipid metabolism both in vivo and in vitro. For in vivo study, four experimental diets - low lipid and low PL diet, as control diet (LL-LP diet, containing 12 % lipid and 1·5 % PL), low-lipid and high-PL diet (containing 12 % lipid and 8 % PL), high-lipid and low-PL diet (HL-LP diet, containing 20 % lipid and 1·5 % PL) and high-lipid and high-PL diet (HL-HP diet, containing 20 % lipid and 8 % PL) - were randomly allocated to four groups of large yellow croaker (Larimichthys crocea) (three cages per group) with similar initial body weight (approximately 8 g)...
December 4, 2017: British Journal of Nutrition
https://www.readbyqxmd.com/read/29196535/wnk1-kinase-and-the-termination-factor-pcf11-connect-nuclear-mrna-export-with-transcription
#15
Adam Volanakis, Kinga Kamieniarz-Gdula, Margarita Schlackow, Nick J Proudfoot
Nuclear gene transcription is coordinated with transcript release from the chromatin template and messenger RNA (mRNA) export to the cytoplasm. Here we describe the role of nuclear-localized kinase WNK1 (with no lysine [K] 1) in the mammalian mRNA export pathway even though it was previously established as a critical regulator of ion homeostasis in the cytoplasm. Our data reveal that WNK1 phosphorylates the termination factor PCF11 on its RNA polymerase II (Pol II) C-terminal domain (CTD)-interacting domain (CID)...
December 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/29196245/novel-potential-photodynamic-therapy-strategy-using-5-aminolevulinic-acid-for-ovarian-clear-cell-carcinoma
#16
Toshiya Teshigawara, Mika Mizuno, Takuya Ishii, Yuya Kitajima, Fumi Utsumi, Jun Sakata, Hiroaki Kajiyama, Kiyosumi Shibata, Masahiro Ishizuka, Fumitaka Kikkawa
BACKGROUND: Photodynamic therapy (PDT) is known as a minimally invasive treatment for cancer. 5-Aminolevulinic acid (ALA) is a precursor of the photosensitizing agent protoporphyrin IX (PpIX). Patients with ovarian clear-cell carcinoma (CCC) have poorer prognoses than those of patients with other histological CCC types. We evaluated the efficacy of ALA-PDT on CCC cells in vitro. METHODS: We used seven human CCC cell lines to measure the cytotoxicity of ALA-PDT. PpIX production in cancer cells was measured using a micro-plate reader...
November 28, 2017: Photodiagnosis and Photodynamic Therapy
https://www.readbyqxmd.com/read/29164525/heat-shock-factor-4-regulates-the-expression-of-hsp25-and-alpha-b-crystallin-by-associating-with-dexd-h-box-rna-helicase-uap56
#17
Xiukun Cui, Wenxiu Han, Jing Li, Riping Feng, Zheng Zhou, JiuLi Han, Mengyuan Li, Shuangfeng Wang, Wanting Zhang, Qin Lei, Jun Zhang, Yutiao Liu, Yanzhong Hu
Heat shock factor 4 controls the transcription of small heat shock proteins (e.g., HSP25, alpha B-cyrstallin, and r-crystallin), that play important roles in modulating lens proteostasis. However, the molecular mechanism underlying HSF4-mediated transcription is still unclear. Using yeast two hybrid, we found that HSF4 interacts with the ATP-dependent DEXD/H-box RNA helicase UAP56, and their interaction in lens epithelial cell line was further confirmed by GST-pull down assay. UAP56 is a vital regulator of pre-mRNA splicing and mature mRNA nuclear export...
November 21, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/29158789/arecoline-increases-glycolysis-and-modulates-ph-regulator-expression-in-ha22t-vgh-hepatoma-cells-leading-to-increase-of-intracellular-ca-2-reactive-oxygen-species-and-anoikis
#18
Hsiao-Ling Cheng, Wen-Tsan Chang, Yu-Chen Hu, Bau-Shan Hsieh, Tzu-Ching Huang, Inn-Wen Chong, Li-Wen Huang, Kee-Lung Chang
Background: Cancer cells proliferate rapidly and are resistant to cell death, relying on aggravated glycolysis to satisfy their increased demand for energy and biosynthetic precursors. However, this process may create unfavorable microenvironments, such as increased acidity, leading to cytotoxicity. Our previous study demonstrated that arecoline induces anoikis of HA22T/VGH hepatoma cells. The present study aimed to examine if arecoline induced anoikis is related to the glycolytic pathway and explore the underlying mechanisms...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29151891/the-exon-junction-complex-factor-y14-is-dynamic-in-the-nucleus-of-the-beetle-tribolium-castaneum-during-late-oogenesis
#19
Artem M Kiselev, Irina S Stepanova, Leonid S Adonin, Florina M Batalova, Vladimir N Parfenov, Dmitry S Bogolyubov, Olga I Podgornaya
Background: The oocyte chromosomes of the red flour beetle, Tribolium castaneum, are gathered into a knot, forming a karyosphere at the diplotene stage of meiotic prophase. Chromatin rearrangement, which is a characteristic feature of oocyte maturation, is well documented. The T. castaneum karyosphere is surrounded by a complex extrachromosomal structure termed the karyosphere capsule. The capsule contains the vast majority of oocyte RNA. We have previously shown using a BrUTP assay that oocyte chromosomes in T...
2017: Molecular Cytogenetics
https://www.readbyqxmd.com/read/29148037/growth-performance-fatty-acid-composition-lipid-deposition-and-hepatic-lipid-metabolism-related-gene-expression-in-juvenile-pond-loach-misgurnus-anguillicaudatus-fed-diets-with-different-dietary-soybean-oil-levels
#20
Y Li, Z Jia, X Liang, D Matulic, M Hussein, J Gao
A 10 week feeding trial was conducted to evaluate the effects of different dietary soybean oil (SO) levels on growth performance, fatty-acid composition and lipid deposition in viscera, histology and histochemistry of liver, intestine and hepatic-lipid metabolism-related gene expressions in pond loach Misgurnus anguillicaudatus juveniles. Misgurnus anguillicaudatus (mean ± s.d. mass 0·40 ± 0·01 g) were fed five experimental diets containing SO at different concentrations: 0, 20, 32, 56 and 100% SO and a diet containing 100% fish oil (100% FO)...
November 17, 2017: Journal of Fish Biology
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