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https://www.readbyqxmd.com/read/28524625/mrna-decay-an-adaptation-tool-for-the-environmental-fungal-pathogen-cryptococcus-neoformans
#1
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/28523359/arginine-cga-codons-as-a-source-of-nonsense-mutations-a-possible-role-in-multivariant-gene-expression-control-of-mrna-quality-and-aging
#2
Georgy A Romanov, Victor S Sukhoverov
Methylation of cytosine residues in DNA of higher eukaryotes, including humans, creates "hot spots" of C→T transitions in the genome. The predominantly methylated sequence in mammalian DNAs is CG (CpG). Among CG-containing codons, CGA codons for arginine are unique due to their ability to create stop codons TGA (UGA in mRNA) upon epigenetic-mediated mutation. As such nonsense mutations can have a strong adverse effect on the cell and organism, we have performed a study, on the example of human genes, aimed to characterise the anticipated effects of epigenetic-mediated nonsense mutations CGA→TGA in somatic cells...
May 18, 2017: Molecular Genetics and Genomics: MGG
https://www.readbyqxmd.com/read/28516114/measurement-of-mrna-decay-in-mouse-embryonic-fibroblasts
#3
Lian-Qun Qiu, Wi S Lai, Deborah J Stumpo, Perry J Blackshear
mRNA stability control is a critical step in the post-transcriptional regulation of gene expression. Actinomycin D, an antibiotic initially used as an anti-cancer drug, has turned out to be a convenient tool for studying the turnover rates of transcripts in cells, due to its inhibition of mRNA synthesis. Here, we describe a protocol for the measurement of mRNA decay after adding actinomycin D into the medium of stable fibroblast cell lines derived from wild-type and tristetraprolin (TTP)-deficient mouse embryonic fibroblast (MEF) cultures, as well as a protocol for determining the relative transcript abundance using semi-quantitative real time RT-PCR...
July 5, 2016: Bio-protocol
https://www.readbyqxmd.com/read/28508407/structural-conservation-of-the-pin-domain-active-site-across-all-domains-of-life
#4
REVIEW
M Senissar, M C Manav, D E Brodersen
The PIN domain (Pil N-terminus) is a compact RNA-binding protein domain present in all domains of life. This 120-residue domain consists of a central and parallel β sheet surrounded by α helices, which together organise 4-5 acidic residues in an active site that binds one or more divalent metal ions and in many cases has endoribonuclease activity. In bacteria and archaea, the PIN domain is primarily associated with toxin-antitoxin loci, consisting of a toxin (the PIN domain nuclease) and an antitoxin that inhibits the function of the toxin under normal growth conditions...
May 15, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28501103/mrna-decay-is-regulated-via-sequestration-of-the-conserved-5-3-exoribonuclease-xrn1-at-eisosome-in-yeast
#5
Katarína Vaškovičová, Thuraya Awadová, Petra Veselá, Mária Balážová, Miroslava Opekarová, Jan Malinsky
We describe a novel mechanism of mRNA decay regulation, which takes place under the conditions of glucose deprivation in the yeast Saccharomyces cerevisiae. The regulation is based on temporally stable sequestration of the main 5'-3' mRNA exoribonuclease Xrn1 at the eisosome, a plasma membrane-associated protein complex organizing a specialized membrane microdomain. As documented by monitoring the decay of a specific mRNA substrate in time, Xrn1-mediated mRNA degradation ceases during the accumulation of Xrn1 at eisosome, but the eisosome-associated Xrn1 retains its functionality and can be re-activated when released to cytoplasm following the addition of glucose...
May 3, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28488892/dcp1a-and-gw182-induce-distinct-cellular-aggregates-and-have-different-effects-on-microrna-pathway
#6
Xiaohui Wang, Liang Chang, Huanru Wang, Airong Su, Zhiwei Wu
AIM: P-bodies are cytoplasmic foci composed of mRNAs and enzymes involved in mRNA degradation. P-bodies have been found to link to RNA interference and RNA decay mediated by microRNAs (miRNAs) and translational repression. Here, we aim to investigate different effects of overexpressed Dcp1a or GW182 on cytoplasmic aggregates formation and influence on miRNA pathway. RESULTS: Small RNAs were recruited into endogenous foci of P-bodies and aggregates formed by Dcpa1 and GW182 overexpression...
May 10, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28486986/the-link-between-adjacent-codon-pairs-and-mrna-stability
#7
Yuriko Harigaya, Roy Parker
BACKGROUND: Evidence in diverse organisms suggests that codon optimality is a major determinant of mRNA translation and degradation. Codon optimality is thought to act by modulating the efficiency of ribosome elongation. In Saccharomyces cerevisiae, a recent study has identified 17 adjacent codon pairs that mediate strong inhibition of translation elongation. However, relationships between the inhibitory codon pairs and other aspects of gene expression are unknown. RESULTS: To gain insights into how the inhibitory codon pairs may affect aspects of gene expression, we utilized existing datasets to conduct genome-scale analyses in S...
May 10, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28475459/regnase-1-is-an-endoribonuclease-essential-for-the-maintenance-of-immune-homeostasis
#8
Takuya Uehata, Osamu Takeuchi
Regnase-1, also known as Zc3h12a or MCPIP1, is responsible for endonucleolytic cleavage of mRNAs encoding proteins involved in inflammatory responses. Furthermore, Regnase-1-mediated mRNA decay (RMD) is critical for the maintenance of immune homeostasis. Regnase-1 controls the magnitude of innate and adaptive immune responses, and thereby dysfunction of this protein in mice leads to the development of spontaneous systemic inflammation. During the last several years, advances have been made in understanding molecular mechanisms of RMD...
May 2017: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/28472401/wig1-is-crucial-for-ago2-mediated-acot7-mrna-silencing-via-mirna-dependent-and-independent-mechanisms
#9
Hyung Chul Lee, Seung Hee Jung, Hyun Jung Hwang, Donghee Kang, Supriyo De, Dawood B Dudekula, Jennifer L Martindale, Byungkyu Park, Seung Kuk Park, Eun Kyung Lee, Jeong-Hwa Lee, Sunjoo Jeong, Kyungsook Han, Heon Joo Park, Young-Gyu Ko, Myriam Gorospe, Jae-Seon Lee
RNA-binding proteins (RBPs) are involved in mRNA splicing, maturation, transport, translation, storage and turnover. Here, we identified ACOT7 mRNA as a novel target of human WIG1. ACOT7 mRNA decay was triggered by the microRNA miR-9 in a WIG1-dependent manner via classic recruitment of Argonaute 2 (AGO2). Interestingly, AGO2 was also recruited to ACOT7 mRNA in a WIG1-dependent manner in the absence of miR-9, which indicates an alternative model whereby WIG1 controls AGO2-mediated gene silencing. The WIG1-AGO2 complex attenuated translation initiation via an interaction with translation initiation factor 5B (eIF5B)...
May 3, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28472342/the-non-stop-decay-mrna-surveillance-pathway-is-required-for-oxidative-stress-tolerance
#10
Nur H Jamar, Paraskevi Kritsiligkou, Chris M Grant
Reactive oxygen species (ROS) are toxic by-products of normal aerobic metabolism. ROS can damage mRNAs and the translational apparatus resulting in translational defects and aberrant protein production. Three mRNA quality control systems monitor mRNAs for translational errors: nonsense-mediated decay, non-stop decay (NSD) and no-go decay (NGD) pathways. Here, we show that factors required for the recognition of NSD substrates and components of the SKI complex are required for oxidant tolerance. We found an overlapping requirement for Ski7, which bridges the interaction between the SKI complex and the exosome, and NGD components (Dom34/Hbs1) which have been shown to function in both NSD and NGD...
May 2, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28463381/rna-binding-proteins-and-their-role-in-the-regulation-of-gene-expression-in-trypanosoma-cruzi-and-saccharomyces-cerevisiae
#11
Camila Oliveira, Helisson Faoro, Lysangela Ronalte Alves, Samuel Goldenberg
RNA-binding proteins (RBPs) have important functions in the regulation of gene expression. RBPs play key roles in post-transcriptional processes in all eukaryotes, such as splicing regulation, mRNA transport and modulation of mRNA translation and decay. RBPs assemble into different mRNA-protein complexes, which form messenger ribonucleoprotein complexes (mRNPs). Gene expression regulation in trypanosomatids occurs mainly at the post-transcriptional level and RBPs play a key role in all processes. However, the functional characterization of RBPs in Trypanosoma cruzi has been impaired due to the lack of reliable reverse genetic manipulation tools...
January 2017: Genetics and Molecular Biology
https://www.readbyqxmd.com/read/28461655/4-thiouridine-labeling-to-analyze-mrna-turnover-in-schizosaccharomyces-pombe
#12
Juan Mata, Jo Ann Wise
Traditionally, the half-lives of mRNAs were measured after inhibition of transcription to allow decay of the preexisting population. The protocol presented here is a more recently developed strategy in which mRNA turnover is analyzed by measuring the decline in levels of newly synthesized RNA labeled with 4-thiouridine (4sU) during a brief pulse. After RNA extraction, the 4sU is biotinylated and the labeled species are purified using streptavidin beads. DNA microarrays can then be used to compare this population with total RNA, allowing half-lives to be calculated...
May 1, 2017: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/28461625/transcript-specific-characteristics-determine-the-contribution-of-endo-and-exonucleolytic-decay-pathways-during-the-degradation-of-nonsense-mediated-decay-substrates
#13
Franziska Ottens, Volker Boehm, Christopher R Sibley, Jernej Ule, Niels H Gehring
Nonsense-mediated mRNA decay (NMD) controls gene expression by eliminating mRNAs with premature or aberrant translation termination. Degradation of NMD substrates is initiated by the central NMD factor UPF1, which recruits the endonuclease SMG6 and the deadenylation-promoting SMG5/7 complex. The extent to which SMG5/7 and SMG6 contribute to the degradation of individual substrates and their regulation by UPF1 remain elusive. Here we map transcriptome-wide sites of SMG6-mediated endocleavage via 3' fragment capture and degradome sequencing...
May 1, 2017: RNA
https://www.readbyqxmd.com/read/28459443/regulated-ire1-dependent-mrna-decay-sets-the-threshold-for-dendritic-cell-survival
#14
Simon J Tavernier, Fabiola Osorio, Lana Vandersarren, Jessica Vetters, Nele Vanlangenakker, Gert Van Isterdael, Karl Vergote, Riet De Rycke, Eef Parthoens, Lianne van de Laar, Takao Iwawaki, Juan R Del Valle, Chih-Chi Andrew Hu, Bart N Lambrecht, Sophie Janssens
The IRE1-XBP1 signalling pathway is part of a cellular programme that protects against endoplasmic reticulum (ER) stress, but also controls development and survival of immune cells. Loss of XBP1 in splenic type 1 conventional dendritic cells (cDC1s) results in functional alterations without affecting cell survival. However, in mucosal cDC1s, loss of XBP1 impaired survival in a tissue-specific manner-while lung cDC1s die, intestinal cDC1s survive. This was not caused by differential activation of ER stress cell-death regulators CHOP or JNK...
May 1, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28456956/role-of-micrornas-in-zygotic-genome-activation-modulation-of-mrna-during-embryogenesis
#15
Alessandro Rosa, Ali H Brivanlou
A fundamental process occurring during early development is the zygotic genome activation, i.e., the initiation of transcription from the embryonic genome. Before that step, cellular processes in the developing embryo are dictated by transcripts produced by the maternal genome and accumulated in the egg during oogenesis. The maternal-to-zygotic transition (MZT) involves both the clearance of maternal RNAs and the initiation of transcription of the embryonic genome and is a tightly regulated process. In some species, decay of maternal transcripts may be facilitated by the activity of microRNAs...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28456689/a-novel-method-for-quantitative-measurements-of-gene-expression-in-single-living-cells
#16
A Mandic, D Strebinger, C Regali, N E Phillips, D M Suter
Gene expression is at the heart of virtually any biological process, and its deregulation is at the source of numerous pathological conditions. While impressive progress has been made in genome-wide measurements of mRNA and protein expression levels, it is still challenging to obtain highly quantitative measurements in single living cells. Here we describe a novel approach based on internal tagging of endogenous proteins with a reporter allowing luminescence and fluorescence time-lapse microscopy. Using luminescence microscopy, fluctuations of protein expression levels can be monitored in single living cells with high sensitivity and temporal resolution over extended time periods...
April 26, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28454348/effects-of-ptcs-on-nonsense-mediated-mrna-decay-are-dependent-on-ptc-location
#17
Heegyum Moon, Xuexiu Zheng, Tiing Jen Loh, Ha Na Jang, Yongchao Liu, Da-Woon Jung, Darren R Williams, Haihong Shen
The récepteur d'origine nantais (RON) gene is a proto-oncogene that is responsible for encoding the human macrophage-stimulating protein (MSP) 1 receptor. MSP activation induces RON-mediated cell dissociation, migration and matrix invasion. Isoforms of RON that exclude exons 5 and 6 encode the RONΔ160 protein, which promotes cell transformation in vitro and tumor metastasis in vivo. Premature termination codons (PTCs) in exons activate the nonsense-mediated mRNA decay (NMD) signaling pathway. The present study demonstrated that PTCs at various locations in the alternative exons 5 and 6 could induce NMD of the majority of the spliced, or partially spliced, isoforms...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28453818/downstream-element-determines-rnase-y-cleavage-of-the-saepqrs-operon-in-staphylococcus-aureus
#18
Gabriella Marincola, Christiane Wolz
In gram-positive bacteria, RNase J1, RNase J2 and RNase Y are thought to be major contributors to mRNA degradation and maturation. In Staphylococcus aureus, RNase Y activity is restricted to regulating the mRNA decay of only certain transcripts. Here the saePQRS operon was used as a model to analyze RNase Y specificity in living cells. A RNase Y cleavage site is located in an intergenic region between saeP and saeQ. This cleavage resulted in rapid degradation of the upstream fragment and stabilization of the downstream fragment...
April 27, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28447221/deleterious-abca7-mutations-and-transcript-rescue-mechanisms-in-early-onset-alzheimer-s-disease
#19
Arne De Roeck, Tobi Van den Bossche, Julie van der Zee, Jan Verheijen, Wouter De Coster, Jasper Van Dongen, Lubina Dillen, Yalda Baradaran-Heravi, Bavo Heeman, Raquel Sanchez-Valle, Albert Lladó, Benedetta Nacmias, Sandro Sorbi, Ellen Gelpi, Oriol Grau-Rivera, Estrella Gómez-Tortosa, Pau Pastor, Sara Ortega-Cubero, Maria A Pastor, Caroline Graff, Håkan Thonberg, Luisa Benussi, Roberta Ghidoni, Giuliano Binetti, Alexandre de Mendonça, Madalena Martins, Barbara Borroni, Alessandro Padovani, Maria Rosário Almeida, Isabel Santana, Janine Diehl-Schmid, Panagiotis Alexopoulos, Jordi Clarimon, Alberto Lleó, Juan Fortea, Magda Tsolaki, Maria Koutroumani, Radoslav Matěj, Zdenek Rohan, Peter De Deyn, Sebastiaan Engelborghs, Patrick Cras, Christine Van Broeckhoven, Kristel Sleegers
Premature termination codon (PTC) mutations in the ATP-Binding Cassette, Sub-Family A, Member 7 gene (ABCA7) have recently been identified as intermediate-to-high penetrant risk factor for late-onset Alzheimer's disease (LOAD). High variability, however, is observed in downstream ABCA7 mRNA and protein expression, disease penetrance, and onset age, indicative of unknown modifying factors. Here, we investigated the prevalence and disease penetrance of ABCA7 PTC mutations in a large early onset AD (EOAD)-control cohort, and examined the effect on transcript level with comprehensive third-generation long-read sequencing...
April 27, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28445691/tis11-mediated-mrna-decay-promotes-the-reacquisition-of-drosophila-intestinal-stem-cell-quiescence
#20
Lindy McClelland, Heinrich Jasper, Benoît Biteau
Adult stem cell proliferation rates are precisely regulated to maintain long-term tissue homeostasis. Defects in the mechanisms controlling stem cell proliferation result in impaired regeneration and hyperproliferative diseases. Many stem cell populations increase proliferation in response to tissue damage and reacquire basal proliferation rates after tissue repair is completed. Although proliferative signals have been extensively studied, much less is known about the molecular mechanisms that restore stem cell quiescence...
April 23, 2017: Developmental Biology
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