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upstream open reading frame

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https://www.readbyqxmd.com/read/28198412/a-screening-strategy-for-the-discovery-of-drugs-that-reduce-c-ebp%C3%AE-lip-translation-with-potential-calorie-restriction-mimetic-properties
#1
Mohamad A Zaini, Christine Müller, Tobias Ackermann, Jeanette Reinshagen, Gertrud Kortman, Ole Pless, Cornelis F Calkhoven
An important part of the beneficial effects of calorie restriction (CR) on healthspan and lifespan is mediated through regulation of protein synthesis that is under control of the mechanistic target of rapamycin complex 1 (mTORC1). As one of its activities, mTORC1 stimulates translation into the metabolic transcription factor CCAAT/Enhancer Binding Protein β (C/EBPβ) isoform Liver-specific Inhibitory Protein (LIP). Regulation of LIP expression strictly depends on a translation re-initiation event that requires a conserved cis-regulatory upstream open reading frame (uORF) in the C/EBPβ-mRNA...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28195124/pervasive-translational-regulation-of-the-cell-signalling-circuitry-underlies-mammalian-development
#2
Kotaro Fujii, Zhen Shi, Olena Zhulyn, Nicolas Denans, Maria Barna
The degree and dynamics of translational control during mammalian development remain poorly understood. Here we monitored translation of the mammalian genome as cells become specified and organize into tissues in vivo. This identified unexpected and pervasive translational regulation of most of the core signalling circuitry including Shh, Wnt, Hippo, PI3K and MAPK pathways. We further identify and functionally characterize a complex landscape of upstream open reading frames (uORFs) across 5'-untranslated regions (UTRs) of key signalling components...
February 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/28191331/development-of-dual-taqman-based-one-step-rrt-pcr-assay-panel-for-rapid-and-accurate-diagnostic-test-of-mers-cov-a-novel-human-coronavirus-ahead-of-hajj-pilgrimage
#3
Mohammad Sadegh Hashemzadeh, Rahimeh Rasouli, Bentolhoda Zahraei, Morteza Izadi, Mahdi Tat, Seyed Hassan Saadat, Mohammad Najarasl, Behzad Khansari Nejad, Ruhollah Dorostkar
BACKGROUND: Coronaviruses (CoVs) are large ribonucleic acid (RNA) viruses causing primarily respiratory disease in humans. A novel human coronavirus, subsequently named middle east respiratory syndrome coronavirus (MERS-CoV), was first reported in Saudi Arabia in September of 2012. With increasing numbers of infections and deaths from MERS-CoV, development of a rapid and reliable kit was crucial to prevent further spread of MERS-CoV. OBJECTIVES: In this study, we present two real-time reverse-transcription polymerase chain reaction (rRT-PCR) assays for in-house rapid and sensitive diagnostic testing of MERS-CoV, detecting the regions upstream of the envelope gene (upE) and open reading frame (ORF) 1b, respectively, for initial screening and final confirmation of MERS-CoV infection, as recommended by the world health organization (WHO)...
November 2016: Iranian Red Crescent Medical Journal
https://www.readbyqxmd.com/read/28190998/quantitative-nucleotide-level-analysis-of-regulation-of-translation-in-response-to-depolarization-of-cultured-neural-cells
#4
Jasbir S Dalal, Chengran Yang, Darshan Sapkota, Allison M Lake, David R O'Brien, Joseph D Dougherty
Studies on regulation of gene expression have contributed substantially to understanding mechanisms for the long-term activity-dependent alterations in neural connectivity that are thought to mediate learning and memory. Most of these studies, however, have focused on the regulation of mRNA transcription. Here, we utilized high-throughput sequencing coupled with ribosome footprinting to globally characterize the regulation of translation in primary mixed neuronal-glial cultures in response to sustained depolarization...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28187409/pgminer-reloaded-fully-automated-proteogenomic-annotation-tool-linking-genomes-to-proteomes
#5
Canan Has, Sergey A Lashin, Alexey V Kochetov, Jens Allmer
Improvements in genome sequencing technology increased the availability of full genomes and transcriptomes of many organisms. However, the major benefit of massive parallel sequencing is to better understand the organization and function of genes which then lead to understanding of phenotypes. In order to interpret genomic data with automated gene annotation studies, several tools are currently available. Even though the accuracy of computational gene annotation is increasing, a combination of multiple lines of experimental evidences should be gathered...
December 18, 2016: Journal of Integrative Bioinformatics
https://www.readbyqxmd.com/read/28092655/circadian-and-upr-dependent-control-of-cpeb4-mediates-a-translational-response-to-counteract-hepatic-steatosis-under-er-stress
#6
Carlos Maillo, Judit Martín, David Sebastián, Maribel Hernández-Alvarez, Mar García-Rocha, Oscar Reina, Antonio Zorzano, Mercedes Fernandez, Raúl Méndez
The cytoplasmic polyadenylation element-binding (CPEB) proteins regulate pre-mRNA processing and translation of CPE-containing mRNAs in early embryonic development and synaptic activity. However, specific functions in adult organisms are poorly understood. Here we show that CPEB4 is required for adaptation to high-fat-diet- and ageing-induced endoplasmic reticulum (ER) stress, and subsequent hepatosteatosis. Stress-activated liver CPEB4 expression is dual-mode regulated. First, Cpeb4 mRNA transcription is controlled by the circadian clock, and then its translation is regulated by the unfolded protein response (UPR) through upstream open reading frames within the 5'UTR...
February 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28057705/translational-control-of-lipogenic-enzymes-in-the-cell-cycle-of-synchronous-growing-yeast-cells
#7
Heidi M Blank, Ricardo Perez, Chong He, Nairita Maitra, Richard Metz, Joshua Hill, Yuhong Lin, Charles D Johnson, Vytas A Bankaitis, Brian K Kennedy, Rodolfo Aramayo, Michael Polymenis
Translational control during cell division determines when cells start a new cell cycle, how fast they complete it, the number of successive divisions, and how cells coordinate proliferation with available nutrients. The translational efficiencies of mRNAs in cells progressing synchronously through the mitotic cell cycle, while preserving the coupling of cell division with cell growth, remain uninvestigated. We now report comprehensive ribosome profiling of a yeast cell size series from the time of cell birth, to identify mRNAs under periodic translational control...
January 5, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28045577/thermospermine-enhances-translation-of-sac51-and-sacl1-in-arabidopsis
#8
Mai Yamamoto, Taku Takahashi
The excessive xylem phenotype of acaulis5 (acl5), an Arabidopsis mutant defective in the synthesis of thermospermine, indicates that thermospermine is required for negative regulation of xylem differentiation. SAC51 was identified from a dominant suppressor of acl5, sac51-d, and encodes a basic helix-loop-helix (bHLH) protein. sac51-d has a premature termination codon in one of upstream open-reading frames (uORFs) of the SAC51 mRNA that is conserved among the SAC51 family members. Thermospermine may act to bypass the inhibitory effect of the uORF on main ORF translation...
January 2, 2017: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/28017601/identification-and-characterization-of-the-sulfazecin-monobactam-biosynthetic-gene-cluster
#9
Rongfeng Li, Ryan A Oliver, Craig A Townsend
The monobactams, exemplified by the natural product sulfazecin, are the only class of β-lactam antibiotics not inactivated by metallo-β-lactamases, which confer bacteria with extended-spectrum β-lactam resistance. We screened a transposon mutagenesis library from Pseudomonas acidophila ATCC 31363 and isolated a sulfazecin-deficient mutant that revealed a gene cluster encoding two non-ribosomal peptide synthetases (NRPSs), a methyltransferase, a sulfotransferase, and a dioxygenase. Three modules and an aberrant C-terminal thioesterase (TE) domain are distributed across the two NRPSs...
January 19, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/27990012/characterization-of-the-traf3ip1-gene-in-yesso-scallop-patinopecten-yessoensis-and-its-expression-in-response-to-bacterial-challenge
#10
Jie Cheng, Jing Wang, Shuyue Wang, Ruojiao Li, Xianhui Ning, Qiang Xing, Xiaoli Ma, Lingling Zhang, Shi Wang, Xiaoli Hu, Zhenmin Bao
Tumor necrosis factor receptor-associated factor 3 (TRAF3) is an important adaptor that transmits upstream activation signals to induce innate immune responses. TRAF3 interacting protein 1 (TRAF3IP1) interacts specifically with TRAF3, but its function in innate immunity remains unclear, especially in marine invertebrates. In this study, to better understand the functions of TRAFs in innate immune responses, we identified and characterized the first bivalve TRAF3IP1 gene, PyTRAF3IP1, from Yesso scallop (Patinopecten yessoensis), one of the most important mollusk species for aquaculture...
December 19, 2016: Genes & Genetic Systems
https://www.readbyqxmd.com/read/27966655/the-5-utr-variant-of-ercc5-fails-to-influence-outcomes-in-ovarian-and-lung-cancer-patients-undergoing-treatment-with-platinum-based-drugs
#11
Eliana Rulli, Federica Guffanti, Elisa Caiola, Monica Ganzinelli, Giovanna Damia, Marina C Garassino, Sheila Piva, Lorenzo Ceppi, Massimo Broggini, Mirko Marabese
The common polymorphic variant in the 5' untranslated region of the excision repair cross-complementation group 5 (ERCC5) gene was described to generate an upstream open reading frame that regulates both the basal ERCC5 expression and its ability to be synthesized following DNA damage. This variant was reported to affect response to platinum therapy in a cohort of patients with pediatric ependymoma. The role of this variant was investigated in two cohorts of cancer patients, specifically in non-small-cell lung cancer (NSCLC) patients (N = 137) and in epithelial ovarian carcinoma (EOC) patients (N = 240), treated in first-line with platinum-based compounds...
December 14, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27956492/screening-for-novel-genes-of-saccharomyces-cerevisiae-involved-in-recombinant-antibody-production
#12
Jorg C de Ruijter, German Jurgens, Alexander D Frey
Cost-effective manufacturing of biopharmaceuticals in non-mammalian hosts still requires tremendous efforts in strain development. In order to expedite identification of novel leads for strain engineering, we used a transposon-mutagenized yeast genomic DNA library to create a collection of Saccharomyces cerevisiae deletion strains expressing a full-length IgG antibody. Using a high-throughput screening, transformants with either significantly higher or lower IgG expression were selected. The integration site of the transposon in three of the selected strains was located by DNA sequencing...
December 11, 2016: FEMS Yeast Research
https://www.readbyqxmd.com/read/27935038/extensive-translational-regulation-during-seed-germination-revealed-by-polysomal-profiling
#13
Bing Bai, Alessia Peviani, Sjors van der Horst, Magdalena Gamm, Berend Snel, Leónie Bentsink, Johannes Hanson
This work investigates the extent of translational regulation during seed germination. The polysome occupancy of each gene is determined by genome-wide profiling of total mRNA and polysome-associated mRNA. This reveals extensive translational regulation during Arabidopsis thaliana seed germination. The polysome occupancy of thousands of individual mRNAs changes to a large extent during the germination process. Intriguingly, these changes are restricted to two temporal phases (shifts) during germination, seed hydration and germination...
December 9, 2016: New Phytologist
https://www.readbyqxmd.com/read/27927164/the-role-of-nucleotide-composition-in-premature-termination-codon-recognition
#14
Fouad Zahdeh, Liran Carmel
BACKGROUND: It is not fully understood how a termination codon is recognized as premature (PTC) by the nonsense-mediated decay (NMD) machinery. This is particularly true for transcripts lacking an exon junction complex (EJC) along their 3' untranslated region (3'UTR), and thus degrade through the EJC-independent NMD pathway. RESULTS: Here, we analyzed data of transcript stability change following NMD repression and identified over 200 EJC-independent NMD-targets...
December 7, 2016: BMC Bioinformatics
https://www.readbyqxmd.com/read/27864472/transcriptome-wide-identification-of-nmd-targeted-human-mrnas-reveals-extensive-redundancy-between-smg6-and-smg7-mediated-degradation-pathways
#15
Martino Colombo, Evangelos D Karousis, Joël Bourquin, Rémy Bruggmann, Oliver Mühlemann
Besides degrading aberrant mRNAs that harbor a premature translation termination codon (PTC), nonsense-mediated mRNA decay (NMD) also targets many seemingly "normal" mRNAs that encode for full-length proteins. To identify a bona fide set of such endogenous NMD targets in human cells, we applied a meta-analysis approach in which we combined transcriptome profiling of knockdowns and rescues of the three NMD factors UPF1, SMG6, and SMG7. We provide evidence that this combinatorial approach identifies NMD-targeted transcripts more reliably than previous attempts that focused on inactivation of single NMD factors...
February 2017: RNA
https://www.readbyqxmd.com/read/27846320/an-inhibitory-motif-on-the-5-utr-of-several-rotavirus-genome-segments-affects-protein-expression-and-reverse-genetics-strategies
#16
Giuditta De Lorenzo, Marija Drikic, Guido Papa, Catherine Eichwald, Oscar R Burrone, Francesca Arnoldi
Rotavirus genome consists of eleven segments of dsRNA, each encoding one single protein. Viral mRNAs contain an open reading frame (ORF) flanked by relatively short untranslated regions (UTRs), whose role in the viral cycle remains elusive. Here we investigated the role of 5'UTRs in T7 polymerase-driven cDNAs expression in uninfected cells. The 5'UTRs of eight genome segments (gs3, gs5-6, gs7-11) of the simian SA11 strain showed a strong inhibitory effect on the expression of viral proteins. Decreased protein expression was due to both compromised transcription and translation and was independent of the ORF and the 3'UTR sequences...
2016: PloS One
https://www.readbyqxmd.com/read/27800707/characterization-of-tilapia-oreochromis-niloticus-aldehyde-reductase-akr1a1-gene-promoter-and-expression-pattern-in-benzo-a-pyrene-exposed-fish
#17
Abeer Hassanin, Yoshio Kaminishi, Takao Itakura
This study planned to isolation and characterization of AKR1A1 cDNA from Bap injected nile tilapia (Oreochromis niloticus), comparison of its characteristic structures with those of other species, characterization of AKR1A1 gene and promoter, and investigation of AKR1A1 mRNA expression in various organs of Bap injected tilapia. The cDNA was 1172 bp long which includes an open reading frame of 975 bp encoding a 324 amino acids protein and a stop codon. The sequence showed 3' and 5' non-coding regions of 179 and 18 bp...
November 1, 2016: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/27790092/upstream-open-reading-frames-located-in-the-leader-of-protein-kinase-m%C3%AE-mrna-regulate-its-translation
#18
Natalia V Bal, Denis Susorov, Ekaterina Chesnokova, Artem Kasianov, Tatiana Mikhailova, Elena Alkalaeva, Pavel M Balaban, Peter Kolosov
For protein synthesis that occurs locally in dendrites, the translational control mechanisms are much more important for neuronal functioning than the transcription levels. Here, we show that uORFs (upstream open reading frames) in the 5' untranslated region (5'UTR) play a critical role in regulation of the translation of protein kinase Mζ (PKMζ). Elimination of these uORFs activates translation of the reporter protein in vitro and in primary cultures of rat hippocampal neurons. Using cell-free translation systems, we demonstrate that translational initiation complexes are formed only on uORFs...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27789685/hnrnps-and-elavl1-cooperate-with-uorfs-to-inhibit-protein-translation
#19
Jiewen Zhang, Lijuan Kong, Sichao Guo, Mengmeng Bu, Qian Guo, Yuan Xiong, Ning Zhu, Chuan Qiu, Xuejing Yan, Qian Chen, Hongfei Zhang, Junling Zhuang, Qiong Wang, Samuel S Zhang, Yan Shen, Meihong Chen
Most of our knowledge about translation regulatory mechanisms comes from studies on lower organisms. However, the translation control system of higher organisms is less understood. Here we find that in 5' untranslated region (5'UTR) of human Annexin II receptor (AXIIR) mRNA, there are two upstream open reading frames (uORFs) acting in a fail-safe manner to inhibit the translation from the main AUG. These uORFs are unfavorable for re-initiation after termination of uORF translation. Heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1), hnRNPA0 and ELAV like RNA binding protein 1 (ELAVL1) bind to the 5'UTR of AXIIR mRNA...
October 26, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27775442/release-kinetics-of-high-sensitivity-cardiac-troponins-i-and-t-and-troponin-t-upstream-open-reading-frame-peptide-tntuorf-in-clinically-induced-acute-myocardial-infarction
#20
Christoph Liebetrau, Luise Gaede, J Sebastian Wolter, Julia Homann, Alexander Meyer, Oliver Dörr, Holger M Nef, Christian Troidl, Christian W Hamm, Helge Möllmann, A Mark Richards, Chris J Pemberton
CONTEXT: Troponin T upstream open reading frame peptide (TnTuORF) may be useful as a novel biomarker in acute cardiac syndromes. OBJECTIVE: The study examined the early release kinetics of TnTuORF. MATERIALS AND METHODS: We analyzed the time course of the release of cardiac troponins I and T and TnTuORF in patients (n = 31) with hypertrophic obstructive cardiomyopathy undergoing transcoronary ablation of septal hypertrophy (TASH). RESULTS: Fifteen minutes after TASH the levels of both troponins increased significantly (cTnT median: 18 ng/L vs...
October 24, 2016: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
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