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EIF4A

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https://www.readbyqxmd.com/read/28918745/coupling-of-translation-initiation-and-termination-does-not-depend-on-the-mode-of-initiation
#1
E A Sogorin, G K Selikhanov, S Ch Agalarov
Recently we described a novel phenomenon observed during eukaryotic translation in a cell-free system: the coupling of initiation and termination on different mRNA molecules. Here we show that the phenomenon does not depend on a special mode of initiation. The mRNAs with certain leader sequences known to require different determinants for successful initiation were examined. Even in a case of using the intergenic internal ribosome entry site (IRES) of cricket paralysis virus RNA as the leader sequence, while no initiation factors are required, the effect of coupling is well expressed, including trials in the presence of hippuristanol as an inhibitor of eIF4A...
July 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28853972/programmed-cell-death-4-mechanism-of-action-the-model-to-be-updated
#2
Polina N Vikhreva, Svetlana V Kalinichenko, Igor V Korobko
Programmed cell death 4 (Pdcd4) is frequently suppressed in tumors of various origins and its suppression correlates with tumor progression. Pdcd4 inhibits cap-dependent translation from mRNAs with highly structured 5'-regions through interaction with the eukaryotic translation initiation factor 4A (eIF4A) helicase and a target transcript. Decrease in Pdcd4 protein is believed to provide a relief of otherwise suppressed eIF4A-dependent translation of proteins facilitating tumor progression. However, it remains unknown if lowered Pdcd4 levels in cells suffices to cause a relief in translation inhibition through appearance of the Pdcd4-free translation-competent eIF4A protein, or more complex and selective mechanisms are involved...
August 30, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28827335/cellular-cap-binding-protein-eif4e-promotes-picornavirus-genome-restructuring-and-translation
#3
Brian C Avanzino, Gabriele Fuchs, Christopher S Fraser
Picornaviruses use internal ribosome entry sites (IRESs) to translate their genomes into protein. A typical feature of these IRESs is their ability to bind directly to the eukaryotic initiation factor (eIF) 4G component of the eIF4F cap-binding complex. Remarkably, the hepatitis A virus (HAV) IRES requires eIF4E for its translation, but no mechanism has been proposed to explain this. Here we demonstrate that eIF4E regulates HAV IRES-mediated translation by two distinct mechanisms. First, eIF4E binding to eIF4G generates a high-affinity binding conformation of the eIF4F complex for the IRES...
August 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28801366/fullerenes-may-cause-eif-mediated-perturbation-in-translational-machinery-evidence-from-in-silico-analysis
#4
Sumbul Firdaus, Anupam Dhasmana, Mohd Wahid, Arshad Jawed, Raju K Mandal, Sajad A Dar, Mohammed Y Areeshi, Mohtashim Lohani, Shafiul Haque
GOALS: Fullerenes have tremendous potential for human biological studies which may further lead to their therapeutic applications. Hence, it has become necessary to explore the possibility of their interference with various important cellular processes. The current study was designed to explore how the presence of fullerenes can affect the binding of DNA with different enzymes and factors involved in transcription and translation process. METHODS: Various bioinformatics approaches and software programs were used to study the effect of fullerenes on the binding pattern of DNA with different enzymes and factors involved in transcription and translation process...
August 2017: Annals of Clinical and Laboratory Science
https://www.readbyqxmd.com/read/28757063/atp-competitive-marine-derived-natural-products-that-target-the-dead-box-helicase-eif4a
#5
Joseph Tillotson, Magdalena Kedzior, Larissa Guimarães, Alison B Ross, Tara L Peters, Andrew J Ambrose, Cody J Schmidlin, Donna D Zhang, Letícia V Costa-Lotufo, Abimael D Rodríguez, Jonathan H Schatz, Eli Chapman
Activation of translation initiation is a common trait of cancer cells. Formation of the heterotrimeric eukaryotic initiation factor F (eIF4F) complex is the rate-limiting step in 5' m7GpppN cap-dependent translation. This trimeric complex includes the eIF4E cap binding protein, the eIF4G scaffolding protein, and the DEAD box RNA helicase eIF4A. eIF4A is an ATP-dependent helicase and because it is the only enzyme in the eIF4F complex, it has been shown to be a potential therapeutic target for a variety of malignancies...
September 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28746394/effects-of-oxidative-and-thermal-stresses-on-stress-granule-formation-in-human-induced-pluripotent-stem-cells
#6
Freshteh Palangi, Samson M Samuel, I Richard Thompson, Chris R Triggle, Mohamed M Emara
Stress Granules (SGs) are dynamic ribonucleoprotein aggregates, which have been observed in cells subjected to environmental stresses, such as oxidative stress and heat shock (HS). Although pluripotent stem cells (PSCs) are highly sensitive to oxidative stress, the role of SGs in regulating PSC self-renewal and differentiation has not been fully elucidated. Here we found that sodium arsenite (SA) and HS, but not hydrogen peroxide (H2O2), induce SG formation in human induced (hi) PSCs. Particularly, we found that these granules contain the well-known SG proteins (G3BP, TIAR, eIF4E, eIF4A, eIF3B, eIF4G, and PABP), were found in juxtaposition to processing bodies (PBs), and were disassembled after the removal of the stress...
2017: PloS One
https://www.readbyqxmd.com/read/28692058/tumor-suppressor-pdcd4-attenuates-sin1-translation-to-inhibit-invasion-in-colon-carcinoma
#7
Q Wang, J Zhu, Y-W Wang, Y Dai, Y-L Wang, C Wang, J Liu, A Baker, N H Colburn, H-S Yang
Programmed cell death 4 (Pdcd4), a tumor invasion suppressor, is frequently downregulated in colorectal cancer and other cancers. In this study, we find that loss of Pdcd4 increases the activity of mammalian target of rapamycin complex 2 (mTORC2) and thereby upregulates Snail expression. Examining the components of mTORC2 showed that Pdcd4 knockdown increased the protein but not mRNA level of stress-activated-protein kinase interacting protein 1 (Sin1), which resulted from enhanced Sin1 translation. To understand how Pdcd4 regulates Sin1 translation, the SIN1 5' untranslated region (5'UTR) was fused with luciferase reporter and named as 5'Sin1-Luc...
July 10, 2017: Oncogene
https://www.readbyqxmd.com/read/28610844/overexpression-of-eif4f-components-in-meningiomas-and-suppression-of-meningioma-cell-growth-by-inhibiting-translation-initiation
#8
Janet L Oblinger, Sarah S Burns, Jie Huang, Li Pan, Yulin Ren, Rulong Shen, A Douglas Kinghorn, D Bradley Welling, Long-Sheng Chang
Meningiomas frequently display activation of the PI3K/AKT/mTOR pathway, leading to elevated levels of phospho-eukaryotic translation initiation factor 4E binding proteins, which enhances protein synthesis; however, it is not known whether inhibition of protein translation is an effective treatment option for meningiomas. We found that human meningiomas expressed high levels of the three components of the eukaryotic initiation factor 4F (eIF4F) translation initiation complex, eIF4A, eIF4E, and eIF4G. The expression of eIF4A and eIF4E was important in sustaining the growth of NF2-deficient benign meningioma Ben-Men-1 cells, as shRNA-mediated knockdown of these proteins strongly reduced cell proliferation...
June 10, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28559306/a-helicase-independent-activity-of-eif4a-in-promoting-mrna-recruitment-to-the-human-ribosome
#9
Masaaki Sokabe, Christopher S Fraser
In the scanning model of translation initiation, the decoding site and latch of the 40S subunit must open to allow the recruitment and migration of messenger RNA (mRNA); however, the precise molecular details for how initiation factors regulate mRNA accommodation into the decoding site have not yet been elucidated. Eukaryotic initiation factor (eIF) 3j is a subunit of eIF3 that binds to the mRNA entry channel and A-site of the 40S subunit. Previous studies have shown that a reduced affinity of eIF3j for the 43S preinitiation complex (PIC) occurs on eIF4F-dependent mRNA recruitment...
June 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28515298/crimean-congo-hemorrhagic-fever-virus-nucleocapsid-protein-augments-mrna-translation
#10
Subbiah Jeeva, Erdong Cheng, Safder S Ganaie, Mohammad A Mir
Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne Nairovirus of the Bunyaviridae family, causing severe illness with high mortality rates in humans. Here, we demonstrate that CCHFV nucleocapsid protein (CCHFV-NP) augments mRNA translation. CCHFV-NP binds to the viral mRNA 5' untranslated region (UTR) with high affinity. It facilitates the translation of reporter mRNA both in vivo and in vitro with the assistance of the viral mRNA 5' UTR. CCHFV-NP equally favors the translation of both capped and uncapped mRNAs, demonstrating the independence of this translation strategy on the 5' cap...
August 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28462052/cloning-and-evaluation-of-reference-genes-for-quantitative-real-time-pcr-analysis-in-amorphophallus
#11
Kai Wang, Yi Niu, Qijun Wang, Haili Liu, Yi Jin, Shenglin Zhang
Quantitative real-time reverse transcription PCR (RT-qPCR) has been widely used in the detection and quantification of gene expression levels because of its high accuracy, sensitivity, and reproducibility as well as its large dynamic range. However, the reliability and accuracy of RT-qPCR depends on accurate transcript normalization using stably expressed reference genes. Amorphophallus is a perennial plant with a high content of konjac glucomannan (KGM) in its corm. This crop has been used as a food source and as a traditional medicine for thousands of years...
2017: PeerJ
https://www.readbyqxmd.com/read/28440616/discovery-and-characterization-of-a-eukaryotic-initiation-factor-4a-3-selective-inhibitor-that-suppresses-nonsense-mediated-mrna-decay
#12
Misa Iwatani-Yoshihara, Masahiro Ito, Yoshihiro Ishibashi, Hideyuki Oki, Toshio Tanaka, Daisuke Morishita, Takashi Ito, Hiromichi Kimura, Yasuhiro Imaeda, Samuel Aparicio, Atsushi Nakanishi, Tomohiro Kawamoto
Eukaryotic initiation factor 4A-3 (eIF4A3) is an Asp-Glu-Ala-Asp (DEAD) box-family adenosine triphosphate (ATP)-dependent RNA helicase. Subtypes eIF4A1 and eIF4A2 are required for translation initiation, but eIF4A3 participates in the exon junction complex (EJC) and functions in RNA metabolism including nonsense-mediated RNA decay (NMD). No small molecules for NMD inhibition via selective inhibition of eIF4A3 have been discovered. Here, we identified allosteric eIF4A3 inhibitors from a high-throughput screening campaign...
May 10, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28439277/expression-of-pennisetum-glaucum-eukaryotic-translational-initiation-factor-4a-pgeif4a-confers-improved-drought-salinity-and-oxidative-stress-tolerance-in-groundnut
#13
Tata Santosh Rama Bhadra Rao, Juturu Vijaya Naresh, Palakolanu Sudhakar Reddy, Malireddy K Reddy, Garladinne Mallikarjuna
Eukaryotic translational initiation factor 4A belong to family of helicases, involved in multifunctional activities during stress and non-stress conditions. The eIF4A gene was isolated and cloned from semi-arid cereal crop of Pennisetum glaucum. In present study, the PgeIF4A gene was expressed under the regulation of stress inducible Arabidopsis rd29A promoter in groundnut (cv JL-24) with bar as a selectable marker. The de-embryonated cotyledons were infected with Agrobacterium tumefaciens (LBA4404) carrying rd29A:PgeIF4A construct and generated high frequency of multiple shoots in phosphinothricin medium...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28242763/eukaryotic-translation-initiation-factor-4g-eif4g-coordinates-interactions-with-eif4a-eif4b-and-eif4e-in-binding-and-translation-of-the-barley-yellow-dwarf-virus-3-cap-independent-translation-element-bte
#14
Pei Zhao, Qiao Liu, W Allen Miller, Dixie J Goss
Barley yellow dwarf virus RNA, lacking a 5' cap and a 3' poly(A) tail, contains a cap-independent translation element (BTE) in the 3'-untranslated region that interacts with host translation initiation factor eIF4G. To determine how eIF4G recruits the mRNA, three eIF4G deletion mutants were constructed: (i) eIF4G601-1196, containing amino acids 601-1196, including the putative BTE-binding region, and binding domains for eIF4E, eIF4A, and eIF4B; (ii) eIF4G601-1488, which contains an additional C-terminal eIF4A-binding domain; and (iii) eIF4G742-1196, which lacks the eIF4E-binding site...
April 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28177284/cap-proximal-nucleotides-via-differential-eif4e-binding-and-alternative-promoter-usage-mediate-translational-response-to-energy-stress
#15
Ana Tamarkin-Ben-Harush, Jean-Jacques Vasseur, Françoise Debart, Igor Ulitsky, Rivka Dikstein
Transcription start-site (TSS) selection and alternative promoter (AP) usage contribute to gene expression complexity but little is known about their impact on translation. Here we performed TSS mapping of the translatome following energy stress. Assessing the contribution of cap-proximal TSS nucleotides, we found dramatic effect on translation only upon stress. As eIF4E levels were reduced, we determined its binding to capped-RNAs with different initiating nucleotides and found the lowest affinity to 5'cytidine in correlation with the translational stress-response...
February 8, 2017: ELife
https://www.readbyqxmd.com/read/28162583/-341-exploring-the-potential-for-an-evolutionarily-conserved-role-for-eif4a-in-pain-plasticity
#16
J Moy, P Ray, E Walters, J Pelletier, T Price
No abstract text is available yet for this article.
April 2016: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28162511/-278-a-potential-role-for-eif4a-in-regulation-of-nociceptor-plasticity-a-motif-based-genome-wide-search-for-eif4a-targets
#17
S Srivastava, S Potla, A Torck, M Zhang, G Dussor, P Ray, T Price
No abstract text is available yet for this article.
April 2016: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28153010/targeting-muc1-c-inhibits-the-akt-s6k1-elf4a-pathway-regulating-tigar-translation-in-colorectal-cancer
#18
Rehan Ahmad, Maroof Alam, Masanori Hasegawa, Yasumitsu Uchida, Omar Al-Obaid, Surender Kharbanda, Donald Kufe
BACKGROUND: Colorectal cancer is third most common malignancy and is the second most common cause of cancer-related death. The MUC1 heterodimeric protein is aberrantly overexpressed in colorectal cancer and has been linked to poor outcomes in this disease. Here, we investigate the effects of the MUC1-C subunit inhibitor (GO-203), which disrupts MUC1-C homo-oligomerization, on human colorectal cancer cells. METHODS: TIGAR mRNA level was determined using qRT-PCR. Western blotting was used to measure TIGAR protein level and AKT-mTOR-S6K1 pathways...
February 2, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28046134/the-triticum-mosaic-virus-5-leader-binds-to-both-eif4g-and-eifiso4g-for-translation
#19
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/28003464/nat1-promotes-translation-of-specific-proteins-that-induce-differentiation-of-mouse-embryonic-stem-cells
#20
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...
January 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
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