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https://www.readbyqxmd.com/read/29238357/structural-and-functional-diversity-of-plant-virus-3-cap-independent-translation-enhancers-3-cites
#1
REVIEW
Verónica Truniger, Manuel Miras, Miguel A Aranda
Most of the positive-strand RNA plant viruses lack the 5'-cap and/or the poly(A)-tail that act synergistically to stimulate canonical translation of cellular mRNAs. However, they have RNA elements in the 5'- or 3'-untranslated regions of their RNAs that are required for their cap-independent translation. Cap-independent translation enhancers (CITEs) have been identified in the genomic 3'-end of viruses belonging to the family Tombusviridae and the genus Luteovirus. Seven classes of 3'-CITEs have been described to date based on their different RNA structures...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29212818/the-histone-demethylase-kdm5a-is-required-for-the-repression-of-astrocytogenesis-and-regulated-by-the-translational-machinery-in-neural-progenitor-cells
#2
Sun-Young Kong, Woosuk Kim, Ha-Rim Lee, Hyun-Jung Kim
Histone demethylases are known to play important roles in the determination of the fate of stem cells and in cancer progression. In this study, we show that the lysine 4 of histone H3 (H3K4), lysine-specific demethylase 5A (KDM5A) is essential for the repression of astrocyte differentiation in neural progenitor cells (NPCs), and its expression is regulated by translational machinery. Knockdown of KDM5A in NPCs increased astrocytogenesis, and conversely, KDM5A overexpression reduced the transcriptional activity of the Gfap promoter...
December 6, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29198077/fibroblast-like-synoviocyte-migration-is-enhanced-by-il-17-mediated-overexpression-of-l-type-amino-acid-transporter-1-lat1-via-the-mtor-4e-bp1-pathway
#3
Zhao Yu, Wang Lin, Zhang Rui, Pan Jihong
In rheumatoid arthritis (RA), activated synovial fibroblasts have the ability to invade joint cartilage, actively contributing to joint destruction in RA. The mechanisms underlying this cell migration and invasion remain unclear. Our previous results and data from the GEO profile indicate that the L-type amino acid transporter gene, LAT1, is overexpressed in the synovium of RA. To identify its potential role in RA, fibroblast-like synoviocytes (FLS) from patients with RA were used to determine the effects of suppressing the LAT1 genes using RNA interference and the LAT inhibitor, BCH...
December 2, 2017: Amino Acids
https://www.readbyqxmd.com/read/29195795/7-methylguanosine-monophosphate-analogues-with-5-1-2-3-triazoyl-moiety-synthesis-and-evaluation-as-the-inhibitors-of-cniiib-nucleotidase
#4
Mateusz Kozarski, Dorota Kubacka, Blazej A Wojtczak, Renata Kasprzyk, Marek R Baranowski, Joanna Kowalska
The hydrolysis of nucleoside 5'-monophosphates to the corresponding nucleosides and inorganic phosphate is catalysed by 5'-nucleotidases, thereby contributing to the control of endogenous nucleotide turnover and affecting the fate of exogenously delivered nucleotide- and nucleoside-derived therapeutics in cells. A recently identified nucleotidase cNIIIB shows preference towards 7-methylguanosine monophosphate (m7GMP) as a substrate, which suggests its potential involvement in mRNA degradation. However, the extent of biological functions and the significance of cNIIIB remains to be elucidated...
November 22, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29192585/yeast-eif4a-enhances-recruitment-of-mrnas-regardless-of-their-structural-complexity
#5
Paul Yourik, Colin Echeverría Aitken, Fujun Zhou, Neha Gupta, Alan G Hinnebusch, Jon R Lorsch
eIF4A is a DEAD-box RNA-dependent ATPase thought to unwind RNA secondary structure in the 5'-untranslated regions (UTRs) of mRNAs to promote their recruitment to the eukaryotic translation pre-initiation complex (PIC). We show that eIF4A's ATPase activity is markedly stimulated in the presence of the PIC, independently of eIF4E•eIF4G, but dependent on subunits i and g of the heteromeric eIF3 complex. Surprisingly, eIF4A accelerated the rate of recruitment of all mRNAs tested, regardless of their degree of structural complexity...
November 30, 2017: ELife
https://www.readbyqxmd.com/read/29166596/the-gcn2-atf4-signaling-pathway-induces-4e-bp-to-bias-translation-and-boost-antimicrobial-peptide-synthesis-in-response-to-bacterial-infection
#6
Deepika Vasudevan, Nicholas K Clark, Jessica Sam, Victoria C Cotham, Beatrix Ueberheide, Michael T Marr, Hyung Don Ryoo
Bacterial infection often leads to suppression of mRNA translation, but hosts are nonetheless able to express immune response genes through as yet unknown mechanisms. Here, we use a Drosophila model to demonstrate that antimicrobial peptide (AMP) production during infection is paradoxically stimulated by the inhibitor of cap-dependent translation, 4E-BP (eIF4E-binding protein; encoded by the Thor gene). We found that 4E-BP is induced upon infection with pathogenic bacteria by the stress-response transcription factor ATF4 and its upstream kinase, GCN2...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29158530/mrnas-containing-nmd-competent-premature-termination-codons-are-stabilized-and-translated-under-upf1-depletion
#7
Won Kyu Kim, SeongJu Yun, Yujin Kwon, Kwon Tae You, Nara Shin, Jiyoon Kim, Hoguen Kim
mRNAs containing premature termination codons (PTCs) are rapidly degraded through nonsense-mediated mRNA decay (NMD). However, some PTC-containing mRNAs evade NMD, and might generate mutant proteins responsible for various diseases, including cancers. Using PTC-containing human genomic β-globin constructs, we show that a fraction (~30%) of PTC-containing mRNAs expressed from NMD-competent PTC-containing constructs were as stable as their PTC-free counterparts in a steady state. These PTC-containing mRNAs were monosome-enriched and rarely contributed to expression of mutant proteins...
November 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29157222/comparative-proteomics-reveals-the-physiological-differences-between-winter-tender-shoots-and-spring-tender-shoots-of-a-novel-tea-camellia-sinensis-l-cultivar-evergrowing-in-winter
#8
Shengjie Liu, Jiadong Gao, Zhongjian Chen, Xiaoyan Qiao, Hualin Huang, Baiyuan Cui, Qingfeng Zhu, Zhangyan Dai, Hualing Wu, Yayan Pan, Chengwei Yang, Jun Liu
BACKGROUND: A recently discovered tea [Camellia sinensis (L.) O. Kuntze] cultivar can generate tender shoots in winter. We performed comparative proteomics to analyze the differentially accumulated proteins between winter and spring tender shoots of this clonal cultivar to reveal the physiological basis of its evergrowing character during winter. RESULTS: We extracted proteins from the winter and spring tender shoots (newly formed two leaves and a bud) of the evergrowing tea cultivar "Dongcha11" respectively...
November 20, 2017: BMC Plant Biology
https://www.readbyqxmd.com/read/29153483/crosstalks-between-translation-and-metabolism-in-cancer
#9
REVIEW
Stefano Biffo, Nicola Manfrini, Sara Ricciardi
Albeit cancer patients' heterogeneity, all tumor cells have alterations of both metabolism and translation. The simplest explanation for this common feature is that several oncogenes coordinate a translational and metabolic reprogramming that is necessary for tumor cells to thrive. Overall, at least three oncogenic pathways, namely c-Myc, RAS and PI3K-mTOR, are known to affect both translation and metabolism by stimulating glycolysis and protein synthesis. The crosstalk between metabolite production and the translational machinery is, instead, less understood...
November 15, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/29139201/defining-the-protein-complexome-of-translation-termination-factor-erf1-identification-of-four-novel-erf1-containing-complexes-that-range-from-20s-to-57s-in-size
#10
Clyde L Denis, Roy Richardson, Shiwha Park, Chongxu Zhang, Wen Xi, Thomas M Laue, Xin Wang
The eukaryotic eRF1 translation termination factor plays an important role in recognizing stop codons and initiating the end to translation. However, which exact complexes contain eRF1 and at what abundance is not clear. We have used analytical ultracentrifugation with fluorescent detection system to identify the protein complexome of eRF1 in the yeast Saccharomyces cerevisiae. In addition to eRF1 presence in translating polysomes, we found that eRF1 associated with five other macromolecular complexes: 77S, 57S, 39S, 28S, and 20S in size...
November 15, 2017: Proteins
https://www.readbyqxmd.com/read/29127434/brd7-regulates-the-insulin-signaling-pathway-by-increasing-phosphorylation-of-gsk3%C3%AE
#11
Lena Golick, Youngah Han, Yoo Kim, Sang Won Park
Reduced hepatic expression levels of bromodomain-containing protein 7 (BRD7) have been suggested to play a role in the development of glucose intolerance in obesity. However, the molecular mechanism by which BRD7 regulates glucose metabolism has remained unclear. Here, we show that BRD7 increases phosphorylation of glycogen synthase kinase 3β (GSK3β) in response to activation of the insulin receptor-signaling pathway shortly after insulin stimulation and the nutrient-sensing pathway after feeding. BRD7 mediates phosphorylation of GSK3β at the Serine 9 residue and this effect on GSK3β occurs even in the absence of AKT activity...
November 10, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29116477/4egi-1-represses-cap-dependent-translation-and-regulates-genome-wide-translation-in-malignant-pleural-mesothelioma
#12
Arpita De, Blake A Jacobson, Mark S Peterson, Joe Jay-Dixon, Marian G Kratzke, Ahad A Sadiq, Manish R Patel, Robert A Kratzke
Deregulation of cap-dependent translation has been implicated in the malignant transformation of numerous human tissues. 4EGI-1, a novel small-molecule inhibitor of cap-dependent translation, disrupts formation of the eukaryotic initiation factor 4F (eIF4F) complex. The effects of 4EGI-1-mediated inhibition of translation initiation in malignant pleural mesothelioma (MPM) were examined. 4EGI-1 preferentially inhibited cell viability and induced apoptosis in MPM cells compared to normal mesothelial (LP9) cells...
November 8, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/29114037/reducing-eif4e-eif4g-interactions-restores-the-balance-between-protein-synthesis-and-actin-dynamics-in-fragile-x-syndrome-model-mice
#13
Emanuela Santini, Thu N Huynh, Francesco Longo, So Yeon Koo, Edward Mojica, Laura D'Andrea, Claudia Bagni, Eric Klann
Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and autism spectrum disorder. FXS is caused by silencing of the FMR1 gene, which encodes fragile X mental retardation protein (FMRP), an mRNA-binding protein that represses the translation of its target mRNAs. One mechanism by which FMRP represses translation is through its association with cytoplasmic FMRP-interacting protein 1 (CYFIP1), which subsequently sequesters and inhibits eukaryotic initiation factor 4E (eIF4E). CYFIP1 shuttles between the FMRP-eIF4E complex and the Rac1-Wave regulatory complex, thereby connecting translational regulation to actin dynamics and dendritic spine morphology, which are dysregulated in FXS model mice that lack FMRP...
November 7, 2017: Science Signaling
https://www.readbyqxmd.com/read/29112301/ribavirin-augments-doxorubicin-s-efficacy-in-human-hepatocellular-carcinoma-through-inhibiting-doxorubicin-induced-eif4e-activation
#14
Jun Tan, Jingfen Ye, Meijun Song, Mi Zhou, Yaoren Hu
Activation of eukaryotic translation initiation factor 4E (eIF4E) is a cellular survival mechanism in response to chemotherapy in cancers. In this work, we demonstrate that targeting eIF4E by ribavirin sensitizes hepatocellular carcinoma (HCC) cell response to doxorubicin. Ribavirin inhibits growth and survival of HCC cells, and to a greater extent than in normal liver cells. Its combination with doxorubicin achieves greater efficacy than single drug in vitro and in vivo. Ribavirin suppresses phosphorylation of molecules involved in Akt/mTOR/eIF4E pathway...
November 7, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/29111978/the-eukaryotic-translation-initiation-factor-eif4e-harnesses-hyaluronan-production-to-drive-its-malignant-activity
#15
Hiba Ahmad Zahreddine, Biljana Culjkovic-Kraljacic, Audrey Emond, Filippa Pettersson, Ronald Midura, Mark Lauer, Sonia Del Rincon, Valbona Cali, Sarit Assouline, Wilson H Miller, Vincent Hascall, Katherine Borden
The microenvironment provides a functional substratum supporting tumour growth. Hyaluronan (HA) is a major component of this structure. While the role of HA in malignancy is well-defined, the mechanisms driving its biosynthesis in cancer are poorly understood. We show that the eukaryotic translation initiation factor eIF4E, an oncoprotein, drives HA biosynthesis. eIF4E stimulates production of enzymes that synthesize the building blocks of HA, UDP-Glucuronic acid and UDP-N-Acetyl-Glucosamine, as well as hyaluronic acid synthase which forms the disaccharide chain...
November 7, 2017: ELife
https://www.readbyqxmd.com/read/29110225/a-deregulated-pi3k-akt-signaling-pathway-in-patients-with-colorectal-cancer
#16
Tao Zhang, Yuanping Ma, Jiansong Fang, Chang Liu, Liangrong Chen
BACKGROUND: Molecular switches in phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway may serve as potential targets for the treatment of colorectal cancer (CRC). This study aims to profile the gene alterations involved in PI3K-AKT signaling pathway in patients with CRC. METHODS: Tumoral and matched peritumoral tissues were collected from 15 CRC patients who went routine surgery. A human PI3K-AKT signaling pathway polymerase chain reaction (PCR) array, which profiled the transcriptional changes of a total number of 84 genes involved in the PI3K-AKT pathway, was then applied to determine the gene alterations in CRC tumoral tissue with matched peritumoral tissue as a healthy control...
November 7, 2017: Journal of Gastrointestinal Cancer
https://www.readbyqxmd.com/read/29100389/targeting-hsp27-eif4e-interaction-with-phenazine-compound-a-promising-alternative-for-castration-resistant-prostate-cancer-treatment
#17
Ziouziou Hajer, Andrieu Claudia, Laurini Erik, Karaki Sara, Fermeglia Maurizio, Oueslati Ridha, Taieb David, Camplo Michel, Siri Olivier, Pricl Sabrina, Katsogiannou Maria, Rocchi Palma
The actual strategy to improve current therapies in advanced prostate cancer involves targeting genes activated by androgen withdrawal, either to delay or prevent the emergence of the castration-refractory phenotype. However, these genes are often implicated in several physiological processes, and long-term inhibition of survival proteins might be accompanied with cytotoxic effects. To avoid this problem, an alternative therapeutic strategy relies on the identification and use of compounds that disrupt specific protein-protein interactions involved in androgen withdrawal...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29093101/vp1-and-vp3-are-required-and-sufficient-for-translation-initiation-of-uncapped-ibdv-genomic-dsrna
#18
Chengjin Ye, Yu Wang, Enli Zhang, Xinpeng Han, Zhaoli Yu, Hebin Liu
Infectious bursal disease virus (IBDV) is a bi-segmented double-strand RNA (dsRNA) virus of the Birnaviridae family. While IBDV genomic dsRNA lacks a 5' cap, the means by which the uncapped IBDV genomic RNA is translated effectively is unknown. In this study, we describe a cap-independent pathway of translation initiation of IBDV uncapped RNA that relies on VP1 and VP3. We show that neither purified IBDV genomic dsRNA nor the uncapped viral plus-sense RNA transcripts was directly translated and rescued into infectious viruses in host cells...
November 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29089021/the-influence-of-micrornas-and-poly-a-tail-length-on-endogenous-mrna-protein-complexes
#19
Olivia S Rissland, Alexander O Subtelny, Miranda Wang, Andrew Lugowski, Beth Nicholson, John D Laver, Sachdev S Sidhu, Craig A Smibert, Howard D Lipshitz, David P Bartel
BACKGROUND: All mRNAs are bound in vivo by proteins to form mRNA-protein complexes (mRNPs), but changes in the composition of mRNPs during posttranscriptional regulation remain largely unexplored. Here, we have analyzed, on a transcriptome-wide scale, how microRNA-mediated repression modulates the associations of the core mRNP components eIF4E, eIF4G, and PABP and of the decay factor DDX6 in human cells. RESULTS: Despite the transient nature of repressed intermediates, we detect significant changes in mRNP composition, marked by dissociation of eIF4G and PABP, and by recruitment of DDX6...
October 31, 2017: Genome Biology
https://www.readbyqxmd.com/read/29078784/dynamic-changes-in-eif4f-mrna-interactions-revealed-by-global-analyses-of-environmental-stress-responses
#20
Joseph L Costello, Christopher J Kershaw, Lydia M Castelli, David Talavera, William Rowe, Paul F G Sims, Mark P Ashe, Christopher M Grant, Simon J Hubbard, Graham D Pavitt
BACKGROUND: Translation factors eIF4E and eIF4G form eIF4F, which interacts with the messenger RNA (mRNA) 5' cap to promote ribosome recruitment and translation initiation. Variations in the association of eIF4F with individual mRNAs likely contribute to differences in translation initiation frequencies between mRNAs. As translation initiation is globally reprogrammed by environmental stresses, we were interested in determining whether eIF4F interactions with individual mRNAs are reprogrammed and how this may contribute to global environmental stress responses...
October 27, 2017: Genome Biology
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