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Cap-dependent translation

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https://www.readbyqxmd.com/read/28095607/heat-shock-protein-70-promotes-coxsackievirus-b3-translation-initiation-and-elongation-via-akt-mtorc1-pathway-depending-on-activation-of-p70s6k-and-cdc2
#1
Fengping Wang, Ye Qiu, Huifang M Zhang, Paul Hanson, Xin Ye, Guangze Zhao Ronald Xie, Lei Tong, Decheng Yang
We previously demonstrated that coxsackievirus B3 (CVB3) infection upregulated heat shock protein 70 (Hsp70) and promoted CVB3 multiplication. Here, we report the underlying mechanism by which Hsp70 enhances viral RNA translation. By using an Hsp70-overexpressing cell line infected with CVB3, we found that Hsp70 enhanced CVB3 VP1 translation at two stages. First, Hsp70 induced upregulation of VP1 translation at the initiation stage via upregulation of IRES trans-acting factor La protein and activation of eIF4E binding protein 1, a cap-dependent translation suppressor...
January 17, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28087764/accumulation-of-polyribosomes-in-dendritic-spine-heads-but-not-bases-and-necks-during-memory-consolidation-depends-on-cap-dependent-translation-initiation
#2
Linnaea E Ostroff, Benjamin Botsford, Sofya Gindina, Kiriana K Cowansage, Joseph E LeDoux, Eric Klann, Charles Hoeffer
: Translation in dendrites is believed to support synaptic changes during memory consolidation. Although translational control mechanisms are fundamental mediators of memory, little is known about their role in local translation. We previously found that polyribosomes accumulate in dendritic spines of the adult rat lateral amygdala (LA) during consolidation of aversive Pavlovian conditioning, and that this memory requires cap-dependent initiation, a primary point of translational control in eukaryotic cells...
January 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28087593/norovirus-mediated-modification-of-the-translational-landscape-via-virus-and-host-induced-cleavage-of-translation-initiation-factors
#3
Edward Emmott, Frederic Sorgeloos, Sarah L Caddy, Surender Vashist, Stanislav Sosnovtsev, Richard Lloyd, Kate Heesom, Nicolas Locker, Ian Goodfellow
Noroviruses produce viral RNAs lacking a 5' cap structure and instead use a virus-encoded VPg protein covalently linked to viral RNA to interact with translation initiation factors and drive viral protein synthesis. Norovirus infection results in the induction of the innate response leading to interferon stimulated gene (ISG) transcription. However the translation of the induced ISG mRNAs is suppressed. A SILAC-based mass spectrometry approach was employed to analyse changes to protein abundance in both whole cell and m7GTP-enriched samples to demonstrate that diminished host mRNA translation correlates with changes to the composition of the eukaryotic initiation factor complex...
January 13, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28079881/translational-upregulation-of-aurora-a-by-hnrnp-q1-contributes-to-cell-proliferation-and-tumorigenesis-in-colorectal-cancer
#4
Chien-Hsien Lai, Yu-Chuan Huang, Jenq-Chang Lee, Joseph Ta-Chien Tseng, Kung-Chao Chang, Yen-Ju Chen, Nai-Jhu Ding, Pao-Hsuan Huang, Wen-Chang Chang, Bo-Wen Lin, Ruo-Yu Chen, Yu-Chu Wang, Yi-Chien Lai, Liang-Yi Hung
By using RNA-immunoprecipitation assay following next-generation sequencing, a group of cell cycle-related genes targeted by hnRNP Q1 were identified, including Aurora-A kinase. Overexpressed hnRNP Q1 can upregulate Aurora-A protein, but not alter the mRNA level, through enhancing the translational efficiency of Aurora-A mRNA, either in a cap-dependent or -independent manner, by interacting with the 5'-UTR of Aurora-A mRNA through its RNA-binding domains (RBDs) 2 and 3. By ribosomal profiling assay further confirmed the translational regulation of Aurora-A mRNA by hnRNP Q1...
January 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28073841/activation-of-eif4e-by-aurora-kinase-a-depicts-a-novel-druggable-axis-in-everolimus-resistant-cancer-cells
#5
Ahmed Katsha, Lihong Wang, Janet Arras, Omar M Omar, Jeffrey A Ecsedy, Abbes Belkhiri, Wael El-Rifai
PURPOSE: In this study, we investigated the role of Aurora kinase A (AURKA) in regulating EIF4E, cap-dependent translation, and resistance to mTOR inhibitor, RAD001 (everolimus). EXPERIMENTAL DESIGN: Tumor xenografts and in vitro cell models of upper gastrointestinal adenocarcinomas (UGCs) were used to determine the role of AURKA in activation of EIF4E and cap-dependent translation. Overexpression, knockdown, and pharmacologic inhibition of AURKA were used in vitro and in vivo...
January 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28060265/analysis-of-cap-binding-proteins-in-human-cells-exposed-to-physiological-oxygen-conditions
#6
Sara Timpano, Gaelan Melanson, Sonia L Evagelou, Brianna D Guild, Erin J Specker, James Uniacke
Translational control is a focal point of gene regulation, especially during periods of cellular stress. Cap-dependent translation via the eIF4F complex is by far the most common pathway to initiate protein synthesis in eukaryotic cells, but stress-specific variations of this complex are now emerging. Purifying cap-binding proteins with an affinity resin composed of Agarose-linked m(7)GTP (a 5' mRNA cap analog) is a useful tool to identify factors involved in the regulation of translation initiation. Hypoxia (low oxygen) is a cellular stress encountered during fetal development and tumor progression, and is highly dependent on translation regulation...
December 28, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28046134/the-triticum-mosaic-virus-5-leader-binds-to-both-eif4g-and-eifiso4g-for-translation
#7
Robyn Roberts, Laura K Mayberry, Karen S Browning, Aurélie M Rakotondrafara
We recently identified a remarkably strong (739 nt-long) IRES-like element in the 5' untranslated region (UTR) of Triticum mosaic virus (TriMV, Potyviridae). Here, we define the components of the cap-binding translation initiation complex that are required for TriMV translation. Using bio-layer interferometry and affinity capture of the native translation apparatus, we reveal that the viral translation element has a ten-fold greater affinity for the large subunit eIF4G/eIFiso4G than to the cap binding protein eIF4E/eIFiso4E...
2017: PloS One
https://www.readbyqxmd.com/read/28031370/binding-of-the-methyl-donor-sam-to-mers-cov-2-o-methyltransferase-nsp16-promotes-the-recruitment-of-the-allosteric-activator-nsp10
#8
Wahiba Aouadi, Alexandre Blanjoie, Jean-Jacques Vasseur, Françoise Debart, Bruno Canard, Etienne Decroly
: The Middle East respiratory syndrome coronavirus (MERS-CoV) non-structural protein 16 (nsp16) is an S-adenosyl-L-methionine (SAM)-dependent 2' -O-methyltransferase (MTase) that is thought to methylate the ribose 2' -OH of the first transcribed nucleotide (N1) of viral RNA cap structures. This 2' -O MTase activity is regulated by nsp10. The 2' -O methylation prevents virus detection by cell innate immunity mechanisms and viral translation inhibition by the interferon-stimulated IFIT-1 protein...
December 28, 2016: Journal of Virology
https://www.readbyqxmd.com/read/28019675/brusatol-overcomes-chemoresistance-through-inhibition-of-protein-translation
#9
Bryan Harder, Wang Tian, James J La Clair, Aik-Choon Tan, Aikseng Ooi, Eli Chapman, Donna D Zhang
The NRF2 pathway activates a cell survival response when cells are exposed to xenobiotics or are under oxidative stress. Therapeutic activation of NRF2 can also be used prior to insult as a means of disease prevention. However, prolonged expression of NRF2 has been shown to protect cancer cells by inducing the metabolism and efflux of chemotherapeutics, leading to both intrinsic and acquired chemoresistance to cancer drugs. This effect has been termed the "dark side" of NRF2. In an effort to combat this chemoresistance, our group discovered the first NRF2 inhibitor, the natural product brusatol, however the mechanism of inhibition was previously unknown...
December 26, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28003464/nat1-promotes-translation-of-specific-proteins-that-induce-differentiation-of-mouse-embryonic-stem-cells
#10
Hayami Sugiyama, Kazutoshi Takahashi, Takuya Yamamoto, Mio Iwasaki, Megumi Narita, Masahiro Nakamura, Tim A Rand, Masato Nakagawa, Akira Watanabe, Shinya Yamanaka
Novel APOBEC1 target 1 (Nat1) (also known as "p97," "Dap5," and "Eif4g2") is a ubiquitously expressed cytoplasmic protein that is homologous to the C-terminal two thirds of eukaryotic translation initiation factor 4G (Eif4g1). We previously showed that Nat1-null mouse embryonic stem cells (mES cells) are resistant to differentiation. In the current study, we found that NAT1 and eIF4G1 share many binding proteins, such as the eukaryotic translation initiation factors eIF3 and eIF4A and ribosomal proteins. However, NAT1 did not bind to eIF4E or poly(A)-binding proteins, which are critical for cap-dependent translation initiation...
December 21, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27994090/a-common-class-of-transcripts-with-5-intron-depletion-distinct-early-coding-sequence-features-and-n1-methyladenosine-modification
#11
Can Cenik, Hon Nian Chua, Guramrit Singh, Abdalla Akef, Michael P Snyder, Alexander F Palazzo, Melissa J Moore, Frederick P Roth
Introns are found in 5' untranslated regions (5'UTRs) for 35% of all human transcripts. These 5'UTR introns are not randomly distributed: genes that encode secreted, membrane-bound and mitochondrial proteins are less likely to have them. Curiously, transcripts lacking 5'UTR introns tend to harbor specific RNA sequence elements in their early coding regions. To model and understand the connection between coding-region sequence and 5'UTR intron status, we developed a classifier that can predict 5'UTR intron status with >80% accuracy using only sequence features in the early coding region...
December 19, 2016: RNA
https://www.readbyqxmd.com/read/27992464/regulation-of-mrna-translation-is-a-novel-mechanism-for-phthalate-toxicity
#12
Jun Ling, Zenaida P Lopez-Dee, Colby Cottell, Laura Wolfe, Derek Nye
Phthalates are a group of plasticizers that are widely used in many consumer products and medical devices, thus generating a huge burden to human health. Phthalates have been known to cause a number of developmental and reproductive disorders functioning as endocrine modulators. They are also involved in carcinogenesis with mechanisms less understood. To further understand the molecular mechanisms of phthalate toxicity, in this study we reported a new effect of phthalates on mRNA translation/protein synthesis, a key regulatory step of gene expression...
2016: PloS One
https://www.readbyqxmd.com/read/27979906/4e-bp-is-a-target-of-the-gcn2-atf4-pathway-during-drosophila-development-and-aging
#13
Min-Ji Kang, Deepika Vasudevan, Kwonyoon Kang, Kyunggon Kim, Jung-Eun Park, Nan Zhang, Xiaomei Zeng, Thomas A Neubert, Michael T Marr, Hyung Don Ryoo
Reduced amino acid availability attenuates mRNA translation in cells and helps to extend lifespan in model organisms. The amino acid deprivation-activated kinase GCN2 mediates this response in part by phosphorylating eIF2α. In addition, the cap-dependent translational inhibitor 4E-BP is transcriptionally induced to extend lifespan in Drosophila melanogaster, but through an unclear mechanism. Here, we show that GCN2 and its downstream transcription factor, ATF4, mediate 4E-BP induction, and GCN2 is required for lifespan extension in response to dietary restriction of amino acids...
2, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/27975086/ligand-responsive-upregulation-of-3-cite-mediated-translation-in-a-wheat-germ-cell-free-expression-system
#14
Atsushi Ogawa, Yuta Murashige, Junichiro Tabuchi, Taiki Omatsu
We have rationally constructed a novel regulation-type of artificial riboswitch that ligand-dose dependently upregulates translation initiation mediated by a 3' cap-independent translation element (3' CITE) with no major hybridization switches in a plant expression system (wheat germ extract).
December 15, 2016: Molecular BioSystems
https://www.readbyqxmd.com/read/27941351/anti-cancer-effect-of-cap-translation-inhibitor-4egi-1-in-human-glioma-u87-cells-involvement-of-mitochondrial-dysfunction-and-er-stress
#15
Ming Wu, Chi Zhang, Xue-Jun Li, Qing Liu, Siyi Wanggou
BACKGROUND: Cancer cells are frequently addicted to deregulated oncogenic protein translation that usually arises as a consequence of increased signaling flux from eIF4F activation. The small molecule 4EG-I, a potent inhibitor of translation initiation through disrupting eIF4E/eIF4G interaction, has been shown to exert anticancer effects in animal models of human cancers. METHODS: Here, we extensively investigated the anticancer activity of 4EGI-1 in human glioma U87 cells...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27934653/leucine-and-mammalian-target-of-rapamycin-dependent-activation-of-muscle-protein-synthesis-in-aging
#16
REVIEW
Jean-Pascal De Bandt
The preservation or restoration of muscle mass is of prime importance for healthy aging. However, aging has been repeatedly shown to be associated with resistance of muscle to the anabolic effects of feeding. Leucine supplementation has been proposed as a possible strategy because of its regulatory role on protein homeostasis. Indeed, it acts independently of growth factors and leads to enhanced cap-dependent mRNA translation initiation and increased protein synthesis. Leucine acts as a signaling molecule directly at the muscle level via the activation of mammalian/mechanistic target of rapamycin complex 1 (mTORC1)...
December 2016: Journal of Nutrition
https://www.readbyqxmd.com/read/27913822/more-than-just-scanning-the-importance-of-cap-independent-mrna-translation-initiation-for-cellular-stress-response-and-cancer
#17
REVIEW
Rafaela Lacerda, Juliane Menezes, Luísa Romão
The scanning model for eukaryotic mRNA translation initiation states that the small ribosomal subunit, along with initiation factors, binds at the cap structure at the 5' end of the mRNA and scans the 5' untranslated region (5'UTR) until an initiation codon is found. However, under conditions that impair canonical cap-dependent translation, the synthesis of some proteins is kept by alternative mechanisms that are required for cell survival and stress recovery. Alternative modes of translation initiation include cap- and/or scanning-independent mechanisms of ribosomal recruitment...
December 2, 2016: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/27911187/fxr1a-associated-micrornp-a-driver-of-specialized-non-canonical-translation-in-quiescent-conditions
#18
Syed I A Bukhari, Shobha Vasudevan
Eukaryotic protein synthesis is a multifaceted process that requires coordination of a set of translation factors in a particular cellular state. During normal growth and proliferation, cells generally make their proteome via conventional translation that utilizes canonical translation factors. When faced with environmental stress such as growth factor deprivation, or in response to biological cues such as developmental signals, cells can have stalled canonical translation. In this situation, cells adapt alternative modes of translation to make specific proteins necessary for required biological functions under these distinct conditions...
December 2, 2016: RNA Biology
https://www.readbyqxmd.com/read/27899653/control-of-the-negative-ires-trans-acting-factor-khsrp-by-ubiquitination
#19
Yu-An Kung, Chuan-Tien Hung, Kun-Yi Chien, Shin-Ru Shih
Cells and viruses can utilize internal ribosome entry sites (IRES) to drive translation when cap-dependent translation is inhibited by stress or viral factors. IRES trans-acting factors (ITAFs) are known to participate in such cap-independent translation, but there are gaps in the understanding as to how ITAFs, particularly negative ITAFs, regulate IRES-driven translation. This study found that Lys109, Lys121 and Lys122 represent critical ubiquitination sites for far upstream element-binding protein 2 (KHSRP, also known as KH-type splicing regulatory protein or FBP2), a negative ITAF...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27899591/modulation-of-nonsense-mediated-decay-by-rapamycin
#20
Rocio T Martinez-Nunez, Andrew Wallace, Doyle Coyne, Linnea Jansson, Miles Rush, Hanane Ennajdaoui, Sol Katzman, Joanne Bailey, Katrin Deinhardt, Tilman Sanchez-Elsner, Jeremy R Sanford
Rapamycin is a naturally occurring macrolide whose target is at the core of nutrient and stress regulation in a wide range of species. Despite well-established roles as an inhibitor of cap-dependent mRNA translation, relatively little is known about its effects on other modes of RNA processing. Here, we characterize the landscape of rapamycin-induced post-transcriptional gene regulation. Transcriptome analysis of rapamycin-treated cells reveals genome-wide changes in alternative mRNA splicing and pronounced changes in NMD-sensitive isoforms...
November 28, 2016: Nucleic Acids Research
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