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mRNA degradation

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https://www.readbyqxmd.com/read/28545761/ultrastructural-analysis-of-human-leukemia-u-937-cells-after-apoptosis-induction-localization-of-proteasomes-and-perichromatin-fibers
#1
Ekaterina S Snigirevskaya, Yan Yu Komissarchik
We studied the ultrastructure of human histiocytic lymphoma U-937cells after apoptosis induction with two external agents, hypertonic shock and etoposide. Appearance of aggregates of particles of nuclear origin within the nuclei and cytoplasm of the induced cells was the first and the most prominent morphological sign of apoptosis. These aggregates were not coated by a membrane, had variable shape, density and size. Two types of particles dominated in the aggregates: perichromatin fibers (PFs) and proteasomes (PRs)...
May 22, 2017: Acta Histochemica
https://www.readbyqxmd.com/read/28545140/the-role-of-the-zinc-finger-protein-zc3h32-in-bloodstream-form-trypanosoma-brucei
#2
Cornelia Klein, Monica Terrao, Christine Clayton
Kinetoplastids rely heavily on post-transcriptional mechanisms for control of gene expression, with regulation of mRNA processing, translation and degradation by RNA-binding proteins. ZC3H32 is a cytosolic mRNA-binding protein with three non-canonical CCCH zinc finger domains. It is much more abundant in bloodstream-form Trypanosoma brucei than in procyclic forms. Tethering of ZC3H32 to a reporter mRNA suppressed translation and resulted in mRNA degradation, and deletion analysis suggested that this activity was present in both the N- and C-terminal domains, but not the central zinc finger-containing domain...
2017: PloS One
https://www.readbyqxmd.com/read/28545085/splicing-factor-sf3b1k700e-mutant-dysregulates-erythroid-differentiation-via-aberrant-alternative-splicing-of-transcription-factor-tal1
#3
Shuiling Jin, Hairui Su, Ngoc-Tung Tran, Jing Song, Sydney S Lu, Ying Li, Suming Huang, Omar Abdel-Wahab, Yanyan Liu, Xinyang Zhao
More than 60% of myeloid dysplasia syndrome (MDS) contains mutations in genes encoding for splicing factors such as SF3B1, U2AF, SRSF2 and ZRSR2. Mutations in SF3B1 are associated with 80% cases of refractory anemia with ring sideroblast (RARS), a subtype of MDS. SF3B1K700E is the most frequently mutated site among mutations on SF3B1. Yet the molecular mechanisms on how mutations of splicing factors lead to defective erythropoiesis are not clear. SF3B1K700E mutant binds to an RNA binding protein, RBM15, stronger than the wild type SF3B1 protein in co-immunoprecipitation assays...
2017: PloS One
https://www.readbyqxmd.com/read/28541906/controlling-mrna-translation
#4
Yoram Zarai, Michael Margaliot, Eduardo Sontag, Tamir Tuller
The ribosomal density along different parts of the coding regions of the mRNA molecule affects various fundamental intracellular phenomena including: protein production rates, global ribosome allocation and organismal fitness, ribosomal drop off, co-translational protein folding, mRNA degradation, and more. Thus, regulating translation in order to obtain a desired ribosomal profile along the mRNA molecule is an important biological problem. We study this problem by using a dynamical model for mRNA translation, called the ribosome flow model (RFM)...
May 23, 2017: IEEE/ACM Transactions on Computational Biology and Bioinformatics
https://www.readbyqxmd.com/read/28540676/micrornas-biomarkers-diagnostics-and-therapeutics
#5
Weili Huang
MicroRNAs (miRNAs) are small noncoding RNAs (21-23 nucleotides in length) that regulate gene expression at translational or posttranslational levels. The major regulatory mechanisms include translational repression or mRNA degradation (Filipowicz et al., Curr Opin Struct Biol 15:331-341, 2005).Aberrant expression of miRNAs has been found to be associated with a variety of human diseases such as cancers/tumors, diabetes, viral infections, cardiovascular diseases, neurodegenerative diseases, and other diseases (Wang et al...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28539657/using-bicistronic-constructs-to-evaluate-the-chaperone-activities-of-heat-shock-proteins-in-cells
#6
Rebecca San Gil, Tracey Berg, Heath Ecroyd
Heat shock proteins (Hsps) are molecular chaperones that prevent the aggregation of client proteins by facilitating their refolding, or trafficking them for degradation. The chaperone activities of Hsps are dependent on dynamic protein-protein interactions, including their oligomerisation into large multi-subunit complexes. Thus, tagging Hsps with fluorescent proteins can interfere with their chaperone activity. To overcome this limitation, we have exploited bicistronic constructs for the concurrent expression of a non-tagged Hsp and fluorescent reporter from a single mRNA in cells...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28539647/physiological-concentrations-of-soluble-uric-acid-are-chondroprotective-and-anti-inflammatory
#7
Jenn-Haung Lai, Shue-Fen Luo, Li-Feng Hung, Chuan-Yueh Huang, Shiu-Bii Lien, Leou-Chyr Lin, Feng-Cheng Liu, B Linju Yen, Ling-Jun Ho
High uric acid levels are a risk factor for cardiovascular disorders and gout; however, the role of physiological concentrations of soluble uric acid (sUA) is poorly understood. This study aimed to clarify the effects of sUA in joint inflammation. Both cell cultures of primary porcine chondrocytes and mice with collagen-induced arthritis (CIA) were examined. We showed that sUA inhibited TNF-α- and interleukin (IL)-1β-induced inducible nitric oxide synthase, cyclooxygenase-2 and matrix metalloproteinase (MMP)-13 expression...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28539224/inhaled-enac-antisense-oligonucleotide-ameliorates-cystic-fibrosis-like-lung-disease-in-mice
#8
Jeff R Crosby, Chenguang Zhao, Chong Jiang, Dong Bai, Melanie Katz, Sarah Greenlee, Hiroshi Kawabe, Michael McCaleb, Daniela Rotin, Shuling Guo, Brett P Monia
BACKGROUND: Epithelial sodium channel (ENaC, Scnn1) hyperactivity in the lung leads to airway surface dehydration and mucus accumulation in cystic fibrosis (CF) patients and in mice with CF-like lung disease. METHODS: We identified several potent ENaC specific antisense oligonucleotides (ASOs) and tested them by inhalation in mouse models of CF-like lung disease. RESULTS: The inhaled ASOs distributed into lung airway epithelial cells and decreased ENaC expression by inducing RNase H1-dependent degradation of the targeted Scnn1a mRNA...
May 20, 2017: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society
https://www.readbyqxmd.com/read/28538180/regnase-1-maintains-iron-homeostasis-via-the-degradation-of-transferrin-receptor-1-and-prolyl-hydroxylase-domain-containing-protein-3-mrnas
#9
Masanori Yoshinaga, Yoshinari Nakatsuka, Alexis Vandenbon, Daisuke Ori, Takuya Uehata, Tohru Tsujimura, Yutaka Suzuki, Takashi Mino, Osamu Takeuchi
Iron metabolism is regulated by transcriptional and post-transcriptional mechanisms. The mRNA of the iron-controlling gene, transferrin receptor 1 (TfR1), has long been believed to be negatively regulated by a yet-unidentified endonuclease. Here, we show that the endonuclease Regnase-1 is critical for the degradation of mRNAs involved in iron metabolism in vivo. First, we demonstrate that Regnase-1 promotes TfR1 mRNA decay. Next, we show that Regnase-1(-/-) mice suffer from severe iron deficiency anemia, although hepcidin expression is downregulated...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28537876/activation-of-perk-branch-of-er-stress-mediates-homocysteine-induced-bkca%C3%A2-channel-dysfunction-in-coronary-artery-via-foxo3a-dependent-regulation-of-atrogin-1
#10
Wen-Tao Sun, Xiang-Chong Wang, Shiu-Kwong Mak, Guo-Wei He, Xiao-Cheng Liu, Malcolm John Underwood, Qin Yang
The molecular mechanism of endoplasmic reticulum (ER) stress in vascular pathophysiology remains inadequately understood. We studied the role of ER stress in homocysteine-induced impairment of coronary dilator function, with uncovering the molecular basis of the effect of ER stress on smooth muscle large-conductance Ca2+-activated K+ (BKCa) channels. The vasodilatory function of BKCa channels was studied in a myograph using endothelium-denuded porcine small coronary arteries. Primary cultured porcine coronary artery smooth muscle cells were used for mRNA and protein measurements and current recording of BKCa channels...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537542/malonate-degradation-in-acinetobacter-baylyi-adp1-operon-organization-and-regulation-by-mdcr
#11
Julie L Stoudenmire, Alicia L Schmidt, Melissa P Tumen-Velasquez, Kathryn T Elliott, Nicole S Laniohan, S Walker Whitley, Nickolaus R Galloway, Melesse Nune, Michael West, Cory Momany, Ellen L Neidle, Anna C Karls
Transcriptional regulators in the LysR or GntR families are typically encoded in the genomic neighbourhood of bacterial genes for malonate degradation. While these arrangements have been evaluated using bioinformatics methods, experimental studies demonstrating co-transcription of predicted operons were lacking. Here, transcriptional regulation was characterized for a cluster of mdc genes that enable a soil bacterium, Acinetobacter baylyi ADP1, to use malonate as a carbon source. Despite previous assumptions that the mdc-gene set forms one operon, our studies revealed distinct promoters in two different regions of a nine-gene cluster...
May 25, 2017: Microbiology
https://www.readbyqxmd.com/read/28537233/-canonical-and-noncanonical-rna-polyadenylation
#12
I G Ustyantsev, J S Golubchikova, O R Borodulina, D A Kramerov
Polyadenylation is the non-template addition of adenosine nucleotides at the 3'-end of RNA, which occurs after transcription and generates a poly(A) tail up to 250-300 nucleotides long. In the first section of our review, we consider the classical process of mRNA 3'-terminus formation, which involves the cleavage of the transcript synthesized by RNA polymerase II and the associated poly(A) tail synthesis by canonical polyadenylate polymerase. Nucleotide sequences needed for mRNA cleavage and poly(A) tail synthesis, in particular the AAUAAA polyadenylation signal, as well as numerous proteins and their complexes involved in mRNA cleavage and polyadenylation, is described in detail...
March 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28536328/-microrna-in-various-aspects-of-cancer-development
#13
Sho Nambara, Koshi Mimori
MicroRNAs(miRNAs)are small(18-25 nucleotides)noncoding RNA molecules that bind to partially complementary mRNA sequences, resulting in target degradation or translation inhibition. A single miRNA can influence the expression of hundreds of target genes, and miRNAs have been implicated as key molecules in various diseases, including cancer. Many studies have shown that the miRNAs play an important role in cancer cells and tumor microenvironment and may be biomarkers for early detection and therapeutic targets for various cancers...
May 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28533900/control-of-gene-expression-through-the-nonsense-mediated-rna-decay-pathway
#14
REVIEW
Andrew Nickless, Julie M Bailis, Zhongsheng You
Nonsense-mediated RNA decay (NMD) was originally discovered as a cellular surveillance pathway that safeguards the quality of mRNA transcripts in eukaryotic cells. In its canonical function, NMD prevents translation of mutant mRNAs harboring premature termination codons (PTCs) by targeting them for degradation. However, recent studies have shown that NMD has a much broader role in gene expression by regulating the stability of many normal transcripts. In this review, we discuss the function of NMD in normal physiological processes, its dynamic regulation by developmental and environmental cues, and its association with human disease...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/28531964/non-electron-transfer-chain-mitochondrial-defects-differently-regulate-hif-1%C3%AE-degradation-and-transcription
#15
Antonina N Shvetsova, Daniela Mennerich, Juha M Kerätär, J Kalervo Hiltunen, Thomas Kietzmann
Mitochondria are the main consumers of molecular O2 in a cell as well as an abundant source of reactive oxygen species (ROS). Both, molecular oxygen and ROS are powerful regulators of the hypoxia-inducible factor-1α-subunit (HIF-α). While a number of mechanisms in the oxygen-dependent HIF-α regulation are quite well known, the view with respect to mitochondria is less clear. Several approaches using pharmacological or genetic tools targeting the mitochondrial electron transport chain (ETC) indicated that ROS, mainly formed at the Rieske cluster of complex III of the ETC, are drivers of HIF-1α activation...
May 8, 2017: Redox Biology
https://www.readbyqxmd.com/read/28524625/mrna-decay-an-adaptation-tool-for-the-environmental-fungal-pathogen-cryptococcus-neoformans
#16
REVIEW
Amanda L M Bloom, Jay Leipheimer, John C Panepinto
Fungi are ubiquitous in the environment and humans constantly encounter them in the soil, air, water, and food. The vast majority of these interactions are inconsequential. However, in the context of immunodeficiency precipitated by HIV infection, hematologic malignancy, or transplantation, a small subset of fungi can cause devastating, systemic infection. The most deadly of the opportunistic environmental fungi, Cryptococcus neoformans, is estimated to cause hundreds of thousands of deaths per year, mostly in the context of HIV co-infection...
May 19, 2017: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/28524086/dietary-green-pea-protects-against-dss-induced-colitis-in-mice-challenged-with-high-fat-diet
#17
Shima Bibi, Luís Fernando de Sousa Moraes, Noelle Lebow, Mei-Jun Zhu
Obesity is a risk factor for developing inflammatory bowel disease. Pea is unique with its high content of dietary fiber, polyphenolics, and glycoproteins, all of which are known to be health beneficial. We aimed to investigate the impact of green pea (GP) supplementation on the susceptibility of high-fat diet (HFD)-fed mice to dextran sulfate sodium (DSS)-induced colitis. Six-week-old C57BL/6J female mice were fed a 45% HFD or HFD supplemented with 10% GP. After 7-week dietary supplementation, colitis was induced by adding 2...
May 18, 2017: Nutrients
https://www.readbyqxmd.com/read/28522867/movement-protein-of-apple-chlorotic-leaf-spot-virus-is-genetically-unstable-and-negatively-regulated-by-ribonuclease-e-in-e-coli
#18
Rahul Mohan Singh, Dharam Singh, Vipin Hallan
Movement protein (MP) of Apple chlorotic leaf spot virus (ACLSV) belongs to "30 K" superfamily of proteins and members of this family are known to show a wide array of functions. In the present study this gene was found to be genetically unstable in E. coli when transformed DH5α cells were grown at 28 °C and 37 °C. However, genetic instability was not encountered at 20 °C. Heterologous over expression failed despite the use of different transcriptional promoters and translational fusion constructs...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28522832/the-fragment-hmga2-sh-3p20-from-hmga2-mrna-3-utr-promotes-the-growth-of-hepatoma-cells-by-upregulating-hmga2
#19
Yuan Wang, Fuquan Chen, Zhe Yang, Man Zhao, Shuqin Zhang, Yuen Gao, Jinyan Feng, Guang Yang, Weiying Zhang, Lihong Ye, Xiaodong Zhang
High mobility group A2 (HMGA2) plays a crucial role in the development of cancer. However, the mechanism by which HMGA2 promotes the growth of hepatocellular carcinoma (HCC) remains unclear. Here, we explore the hypothesis that HMGA2 may enhance the growth of hepatoma cells through a fragment based on the secondary structure of HMGA2 mRNA 3'-untranslated region (3'UTR). Bioinformatics analysis showed that HMGA2 mRNA displayed a hairpin structure within its 3'UTR, termed HMGA2-sh. Mechanistically, RNA immunoprecipitation assays showed that the microprocessor Drosha or DGCR8 interacted with HMGA2 mRNA in hepatoma cells...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28522392/low-molecular-weight-mannogalactofucans-prevent-herpes-simplex-virus-type-1-infection-via-activation-of-toll-like-receptor-2
#20
Woo Jung Kim, Ji Won Choi, Won Jong Jang, Young-Sun Kang, Chang Won Lee, Andriy Synytsya, Yong Il Park
Low-molecular-weight mannogalactofucans (LMMGFs, <4000g/mol) were prepared by the enzymatic degradation of Undaria pinnatifida sporophyll galactofucan (MF) and evaluated or their antiviral activities and underlying action mechanisms against herpes simplex virus type 1 (HSV-1). The 50% inhibitory concentrations (IC50) of LMMGFs and MF were 2.64 and 2.42μg/mL, respectively. LMMGFs inhibited the viral entry on the host cell surface and also exhibited inhibitory activity directly against viral particles, as observed in a virucidal assay...
May 15, 2017: International Journal of Biological Macromolecules
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