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https://www.readbyqxmd.com/read/28279185/constitutively-stressed-yeast-strains-are-high-yielding-for-recombinant-fps1-implications-for-the-translational-regulation-of-an-aquaporin
#1
Stephanie P Cartwright, Richard A J Darby, Debasmita Sarkar, Nicklas Bonander, Stephane R Gross, Mark P Ashe, Roslyn M Bill
BACKGROUND: We previously selected four strains of Saccharomyces cerevisiae for their ability to produce the aquaporin Fps1 in sufficient yield for further study. Yields from the yeast strains spt3Δ, srb5Δ, gcn5Δ and yTHCBMS1 (supplemented with 0.5 μg/mL doxycycline) that had been transformed with an expression plasmid containing 249 base pairs of 5' untranslated region (UTR) in addition to the primary FPS1 open reading frame (ORF) were 10-80 times higher than yields from wild-type cells expressing the same plasmid...
March 9, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28260789/hbz-mediated-shift-of-jund-from-growth-suppressor-to-tumor-promoter-in-leukemic-cells-by-inhibition-of-ribosomal-protein-s25-expression
#2
M Terol, H Gazon, I Lemasson, M Duc Dodon, B Barbeau, R Césaire, J-M Mesnard, J-M Péloponèse
HTLV-1 bZIP factor (HBZ) is a key player in proliferation and transformation of HTLV-1-infected cells, thus contributing to ATL development. HBZ deregulates gene expression within the host cell by interacting with several cellular partners. Through its C-terminal ZIP domain, HBZ is able to contact and activate JunD, a transcription factor of the AP-1 family. jund mRNA is intronless but can generate two protein isoforms by alternative translation initiation: JunD full-length and ΔJunD, an N-terminal truncated form unresponsive to the tumor suppressor menin...
March 6, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28260621/differential-regulation-of-hepatitis-b-virus-core-protein-expression-and-genome-replication-by-a-small-upstream-open-reading-frame-and-naturally-occurring-mutations-in-the-precore-region
#3
Li Zong, Yanli Qin, Haodi Jia, Lei Ye, Yongxiang Wang, Jiming Zhang, Jack R Wands, Shuping Tong, Jisu Li
Hepatitis B virus (HBV) transcribes two subsets of 3.5-kb RNAs: precore RNA for hepatitis B e antigen (HBeAg) expression, and pregenomic RNA for core and P protein translation as well as genome replication. HBeAg expression could be prevented by mutations in the precore region, while an upstream open reading frame (uORF) has been proposed as a negative regulator of core protein translation. We employed replication competent HBV DNA constructs and transient transfection experiments in Huh7 cells to verify the uORF effect and to explore the alternative function of precore RNA...
March 2, 2017: Virology
https://www.readbyqxmd.com/read/28246118/gtpase-rop2-binds-and-promotes-activation-of-target-of-rapamycin-tor-in-response-to-auxin
#4
Mikhail Schepetilnikov, Joelle Makarian, Ola Srour, Angèle Geldreich, Zhenbiao Yang, Johana Chicher, Philippe Hammann, Lyubov A Ryabova
Target of rapamycin (TOR) promotes reinitiation at upstream ORFs (uORFs) in genes that play important roles in stem cell regulation and organogenesis in plants. Here, we report that the small GTPase ROP2, if activated by the phytohormone auxin, promotes activation of TOR, and thus translation reinitiation of uORF-containing mRNAs. Plants with high levels of active ROP2, including those expressing constitutively active ROP2 (CA-ROP2), contain high levels of active TOR ROP2 physically interacts with and, when GTP-bound, activates TOR in vitro TOR activation in response to auxin is abolished in ROP-deficient rop2 rop6 ROP4 RNAi plants...
February 28, 2017: EMBO Journal
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
#5
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
#6
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/28158752/hnrnps-and-elavl1-cooperate-with-uorfs-to-inhibit-protein-translation
#7
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
No abstract text is available yet for this article.
October 25, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/28119417/in-vivo-evidence-that-eif3-stays-bound-to-ribosomes-elongating-and-terminating-on-short-upstream-orfs-to-promote-reinitiation
#8
Mahabub Pasha Mohammad, Vanda Munzarová Pondělíčková, Jakub Zeman, Stanislava Gunišová, Leoš Shivaya Valášek
Translation reinitiation is a gene-specific translational control mechanism characterized by the ability of some short upstream ORFs to prevent recycling of the post-termination 40S subunit in order to resume scanning for reinitiation downstream. Its efficiency decreases with the increasing uORF length, or by the presence of secondary structures, suggesting that the time taken to translate a uORF is more critical than its length. This led to a hypothesis that some initiation factors needed for reinitiation are preserved on the 80S ribosome during early elongation...
January 23, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28094500/chronic-mild-stress-induced-alterations-of-local-protein-synthesis-a-role-for-cognitive-impairment
#9
Francesca Calabrese, Paola Brivio, Piotr Gruca, Magdalena Lason-Tyburkiewicz, Mariusz Papp, Marco A Riva
Depression, a major cause of disability worldwide, is characterized by a complex and heterogeneous symptomatology. With this respect, cognitive deterioration represents a major problem that has a strong impact on a patient's function. Thus, within the context of a depressive phenotype, it is important to characterize the mechanisms that sustain cognitive dysfunctions and may represent an important target for pharmacological intervention. Here, using the chronic mild stress (CMS) paradigm of depression, we found that, independently from the anhedonic phenotype, CMS rats showed a deficit in the novel object recognition (NOR) test, which is associated with an inability to phosphorylate GluN2B subunit on Ser1303 and to activate the mTOR pathway...
February 3, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28057705/translational-control-of-lipogenic-enzymes-in-the-cell-cycle-of-synchronous-growing-yeast-cells
#10
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
#11
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/27864472/transcriptome-wide-identification-of-nmd-targeted-human-mrnas-reveals-extensive-redundancy-between-smg6-and-smg7-mediated-degradation-pathways
#12
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/27790092/upstream-open-reading-frames-located-in-the-leader-of-protein-kinase-m%C3%AE-mrna-regulate-its-translation
#13
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
#14
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/27760805/the-minimum-open-reading-frame-aug-stop-induces-boron-dependent-ribosome-stalling-and-mrna-degradation
#15
Mayuki Tanaka, Naoyuki Sotta, Yusuke Yamazumi, Yui Yamashita, Kyoko Miwa, Katsunori Murota, Yukako Chiba, Masami Yokota Hirai, Tetsu Akiyama, Hitoshi Onouchi, Satoshi Naito, Toru Fujiwara
Upstream open reading frames (uORFs) are often translated ahead of the main ORF of a gene and regulate gene expression, sometimes in a condition-dependent manner, but such a role for the minimum uORF (hereafter referred to as AUG-stop) in living organisms is currently unclear. Here, we show that AUG-stop plays an important role in the boron (B)-dependent regulation of NIP5;1, encoding a boric acid channel required for normal growth under low B conditions in Arabidopsis thaliana High B enhanced ribosome stalling at AUG-stop, which was accompanied by the suppression of translation and mRNA degradation...
November 2016: Plant Cell
https://www.readbyqxmd.com/read/27742800/global-analysis-of-truncated-rna-ends-reveals-new-insights-into-ribosome-stalling-in-plants
#16
Cheng-Yu Hou, Wen-Chi Lee, Hsiao-Chun Chou, Ai-Ping Chen, Shu-Jen Chou, Ho-Ming Chen
High-throughput approaches for profiling the 5' ends of RNA degradation intermediates on a genome-wide scale are frequently applied to analyze and validate cleavage sites guided by microRNAs (miRNAs). However, the complexity of the RNA degradome other than miRNA targets is currently largely uncharacterized, and this limits the application of RNA degradome studies. We conducted a global analysis of 5'-truncated mRNA ends that mapped to coding sequences (CDSs) of Arabidopsis thaliana, rice (Oryza sativa), and soybean (Glycine max)...
October 2016: Plant Cell
https://www.readbyqxmd.com/read/27526386/arabidopsis-polyamine-oxidase-2-uorf-is-required-for-downstream-translational-regulation
#17
María de la Luz Guerrero-González, María Azucena Ortega-Amaro, Margarita Juárez-Montiel, Juan Francisco Jiménez-Bremont
In eukaryotic mRNAs, small upstream open reading frames (uORFs) located in the 5'-untranslated region control the translation of the downstream main ORF. Polyamine oxidase (PAO) enzymes catalyze the oxidation of higher polyamines such as spermidine and spermine, and therefore contribute to the maintenance of intracellular polyamine content and to the regulation of physiological processes through their catabolic products. Recently, we reported that the Arabidopsis thaliana Polyamine Oxidase 2 (AtPAO2) is post-transcriptionally regulated by its 5'-UTR region through an uORF...
November 2016: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/27467758/5-terminal-augs-in-escherichia-coli-mrnas-with-shine-dalgarno-sequences-identification-and-analysis-of-their-roles-in-non-canonical-translation-initiation
#18
Heather J Beck, Ian M C Fleming, Gary R Janssen
Analysis of the Escherichia coli transcriptome identified a unique subset of messenger RNAs (mRNAs) that contain a conventional untranslated leader and Shine-Dalgarno (SD) sequence upstream of the gene's start codon while also containing an AUG triplet at the mRNA's 5'- terminus (5'-uAUG). Fusion of the coding sequence specified by the 5'-terminal putative AUG start codon to a lacZ reporter gene, as well as primer extension inhibition assays, reveal that the majority of the 5'-terminal upstream open reading frames (5'-uORFs) tested support some level of lacZ translation, indicating that these mRNAs can function both as leaderless and canonical SD-leadered mRNAs...
2016: PloS One
https://www.readbyqxmd.com/read/27398791/translation-efficiency-of-mrnas-is-increased-by-antisense-oligonucleotides-targeting-upstream-open-reading-frames
#19
Xue-Hai Liang, Wen Shen, Hong Sun, Michael T Migawa, Timothy A Vickers, Stanley T Crooke
Increasing the levels of therapeutic proteins in vivo remains challenging. Antisense oligonucleotides (ASOs) are often used to downregulate gene expression or to modify RNA splicing, but antisense technology has not previously been used to directly increase the production of selected proteins. Here we used a class of modified ASOs that bind to mRNA sequences in upstream open reading frames (uORFs) to specifically increase the amounts of protein translated from a downstream primary ORF (pORF). Using ASO treatment, we increased the amount of proteins expressed from four genes by 30-150% in a dose-dependent manner in both human and mouse cells...
August 2016: Nature Biotechnology
https://www.readbyqxmd.com/read/27388339/the-sac51-family-plays-a-central-role-in-thermospermine-responses-in-arabidopsis
#20
Qingqing Cai, Hiroko Fukushima, Mai Yamamoto, Nami Ishii, Tomoaki Sakamoto, Tetsuya Kurata, Hiroyasu Motose, Taku Takahashi
The acaulis5 (acl5) mutant of Arabidopsis thaliana is defective in the biosynthesis of thermospermine and shows a dwarf phenotype associated with excess xylem differentiation. SAC51 was identified from a dominant suppressor of acl5, sac51-d, and encodes a basic helix-loop-helix protein. The sac51-d mutant has a premature termination codon in an upstream open reading frame (uORF) that is conserved among all four members of the SAC51 family, SAC51 and SACL1-SACL3 This suggests that thermospermine cancels the inhibitory effect of the uORF in main ORF translation...
August 2016: Plant & Cell Physiology
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