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https://www.readbyqxmd.com/read/29786657/eukaryotic-translation-initiation-factor-4a-down-regulation-mediates-interleukin-24-induced-apoptosis-through-inhibition-of-translation
#1
Xuelin Zhong, Leah Persaud, Hilal Muharam, Ashleigh Francis, Dibash Das, Bertal Huseyin Aktas, Moira Sauane
Dysregulated activity of helicase eIF4A drives transformation to and maintenance of cancer cell phenotype by reprogramming cellular translation. Interleukin 24 (IL-24) is a tumor-suppressing protein, which has the ability to inhibit angiogenesis, sensitize cancer cells to chemotherapy, and induce cancer cell-specific apoptosis. In this study, we found that eIF4A is inhibited by IL-24. Consequently, selective reduction of translation was observed for mRNAs harboring strong secondary structures in their 5'-untranslated regions (5'UTRs)...
May 22, 2018: Cancers
https://www.readbyqxmd.com/read/29774448/the-expression-alteration-of-bc1-rna-and-its-interaction-with-eukaryotic-translation-initiation-factor-eif4a-post-status-epilepticus
#2
Xiangchang Zeng, Wenjing Zong, Qing Gao, Siyu Chen, Lulu Chen, Guirong Zeng, Weihua Huang, Zhenyu Li, Chang Zeng, Yuanyuan Xie, Xiaohui Li, Bo Xiao, Dongsheng-Ouyang, Kai Hu
Abnormal dendritic sprouting and synaptic remodelling are important pathological features of temporal lobe epilepsy. BC1 RNA is a translation repressor involved in the regulation of the dendritic protein synthesis and mRNA transport, which is essential for dendritic development and plasticity. The expression alteration of BC1 RNA in the pilocarpine induced epilepsy model remains unknown. It is unclear if the interactions between BC1 RNA and eukaryotic initiation factor 4A (eIF4A) exists in this model. The purpose of this study was to investigate the expression changes of BC1 RNA and its interactions with eIF4A post-status epilepticus (SE)...
May 17, 2018: Neurochemical Research
https://www.readbyqxmd.com/read/29700118/the-3-mrna-i-shaped-structure-of-maize-necrotic-streak-virus-binds-to-eukaryotic-translation-factors-for-eif4f-mediated-translation-initiation
#3
Qiao Liu, Dixie J Goss
Unlike the mRNAs of their eukaryotic hosts, many RNAs of viruses lack a 5' m7GpppN cap and the 3' polyadenosine tail, and yet they are translated efficiently. Plant RNA viruses, in particular, have complex structures within their mRNA UTRs that allow them to bypass some cellular translation control steps. In the 3' UTR of maize necrotic streak virus (MNeSV), an I-shaped RNA structure (ISS) has been shown to bind eukaryotic initiation factor eIF4F and to mediate viral translation initiation. A 5'-3' RNA "kissing-loop" interaction is required for optimal translation...
April 26, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29695414/mtorc1-is-transiently-reactivated-in-injured-nerves-to-promote-c-jun-elevation-and-schwann-cell-dedifferentiation
#4
Camilla Norrmén, Gianluca Figlia, Patrick Pfistner, Jorge A Pereira, Sven Bachofner, Ueli Suter
Schwann cells (SCs) are endowed with a remarkable plasticity. When peripheral nerves are injured, SCs dedifferentiate and acquire new functions to coordinate nerve repair as so-called repair SCs. Subsequently, SCs redifferentiate to remyelinate regenerated axons. Given the similarities between SC de/redifferentiation in injured nerves and in demyelinating neuropathies, elucidating the signals involved in SC plasticity after nerve injury has potentially wider implications. c-Jun has emerged as a key transcription factor regulating SC dedifferentiation and the acquisition of repair SC features...
April 25, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29669014/eukaryotic-translation-initiation-factor-4aii-contributes-to-microrna-122-regulation-of-hepatitis-c-virus-replication
#5
Choudhary Shoaib Ahmed, Poppy L Winlow, Aimee L Parsons, Catherine L Jopling
Hepatitis C virus (HCV) is a positive sense RNA virus that persistently infects human liver, leading to cirrhosis and hepatocellular carcinoma. HCV replication requires the liver-specific microRNA-122 (miR-122). In contrast to canonical miRNA-mediated repression via 3'UTR sites, miR-122 positively regulates HCV replication by a direct interaction with the 5' untranslated region (UTR) of the viral RNA. The protein factor requirements for this unusual miRNA regulation remain poorly understood. Here, we identify eIF4AII, previously implicated in miRNA-mediated repression via 3'UTR sites, as a host factor that is important for HCV replication...
April 14, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29584632/inhibition-of-zika-virus-replication-by-silvestrol
#6
Fabian Elgner, Catarina Sabino, Michael Basic, Daniela Ploen, Arnold Grünweller, Eberhard Hildt
The Zika virus (ZIKV) outbreak in 2016 in South America with specific pathogenic outcomes highlighted the need for new antiviral substances with broad-spectrum activities to react quickly to unexpected outbreaks of emerging viral pathogens. Very recently, the natural compound silvestrol isolated from the plant Aglaia foveolata was found to have very potent antiviral effects against the (-)-strand RNA-virus Ebola virus as well as against Corona- and Picornaviruses with a (+)-strand RNA-genome. This antiviral activity is based on the impaired translation of viral RNA by the inhibition of the DEAD-box RNA helicase eukaryotic initiation factor-4A (eIF4A) which is required to unwind structured 5´-untranslated regions (5'-UTRs) of several proto-oncogenes and thereby facilitate their translation...
March 27, 2018: Viruses
https://www.readbyqxmd.com/read/29514904/experimental-analysis-of-mimivirus-translation-initiation-factor-4a-reveals-its-importance-in-viral-protein-translation-during-infection-of-acanthamoeba-polyphaga
#7
Meriem Bekliz, Said Azza, Hervé Seligmann, Philippe Decloquement, Didier Raoult, Bernard La Scola
The Acanthamoeba polyphaga mimivirus is the first giant virus ever described, with a 1.2-Mb genome which encodes 979 proteins, including central components of the translation apparatus. One of these proteins, R458, was predicted to initiate translation, although its specific role remains unknown. We silenced the R458 gene using small interfering RNA (siRNA) and compared levels of viral fitness and protein expression in silenced versus wild-type mimivirus. Silencing decreased the growth rate, but viral particle production at the end of the viral cycle was unaffected...
May 15, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29512632/-mutant-initiation-factor-eif4a-r362q-does-not-suppress-the-assembly-of-the-48s-preinitiation-complex-on-mrna-with-the-leader-sequence-of-mrna-that-encodes-for-obelin
#8
P A Sakharov, S Ch Agalarov
The formation of ribosomal 48S initiation complexes at the start codon of the mRNA leader sequence that encodes obelin has been studied using the method of primer extension inhibition (toeprinting). Experiments have been performed in a system composed of purified individual components required to initiate translation. The influence of the dominant negative mutant of factor eIF4A (R362Q) on translation initiation has been studied. It has been shown that the presence of the mutant in reaction mixture has no effect on efficiency of formation of the 48S complexes at start codon of the template studied...
January 2018: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/29487587/the-initiation-factors-eif2-eif2a-eif2d-eif4a-and-eif4g-are-not-involved-in-translation-driven-by-hepatitis-c-virus-ires-in-human-cells
#9
Esther González-Almela, Hugh Williams, Miguel A Sanz, Luis Carrasco
Animal viruses have evolved a variety of strategies to ensure the efficient translation of their mRNAs. One such strategy is the use of internal ribosome entry site (IRES) elements, which circumvent the requirement for some eukaryotic initiation factors (eIFs). Much effort has been directed to unravel the precise mechanism of translation initiation by hepatitis C virus (HCV) mRNA. In the present study, we examined the involvement of several eIFs in HCV IRES-driven translation in human cells in a comparative analysis with mRNAs bearing the encephalomyocarditis virus or the Cricket paralysis virus IRES element...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29471358/eif4a-alleviates-the-translational-repression-mediated-by-classical-secondary-structures-more-than-by-g-quadruplexes
#10
Joseph A Waldron, Farheen Raza, John Le Quesne
Increased activity of the mRNA helicase eIF4A drives cellular malignancy by reprogramming cellular translation, and eIF4A activity is the direct or indirect target of many emerging cancer therapeutics. The enriched presence of (GGC)4 motifs, which have the potential to fold into two-layered G-quadruplexes, within the 5'UTRs of eIF4A-dependent mRNAs suggests that eIF4A is required for the unwinding of these structures within these eIF4A-controlled mRNAs. However, the existence of folded G-quadruplexes within cells remains controversial, and G-quadruplex folding is in direct competition with classical Watson-Crick based secondary structures...
April 6, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29463745/rocaglates-as-dual-targeting-agents-for-experimental-cerebral-malaria
#11
David Langlais, Regina Cencic, Neda Moradin, James M Kennedy, Kodjo Ayi, Lauren E Brown, Ian Crandall, Michael J Tarry, Martin Schmeing, Kevin C Kain, John A Porco, Jerry Pelletier, Philippe Gros
Cerebral malaria (CM) is a severe and rapidly progressing complication of infection by Plasmodium parasites that is associated with high rates of mortality and morbidity. Treatment options are currently few, and intervention with artemisinin (Art) has limited efficacy, a problem that is compounded by the emergence of resistance to Art in Plasmodium parasites. Rocaglates are a class of natural products derived from plants of the Aglaia genus that have been shown to interfere with eukaryotic initiation factor 4A (eIF4A), ultimately blocking initiation of protein synthesis...
March 6, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29419763/the-regulation-of-translation-in-alphavirus-infected-cells
#12
REVIEW
Luis Carrasco, Miguel Angel Sanz, Esther González-Almela
Sindbis virus (SINV) contains an RNA genome of positive polarity with two open reading frames (ORFs). The first ORF is translated from the genomic RNA (gRNA), rendering the viral non-structural proteins, whereas the second ORF is translated from a subgenomic mRNA (sgRNA), which directs the synthesis of viral structural proteins. SINV infection strongly inhibits host cell translation through a variety of different mechanisms, including the phosphorylation of the eukaryotic initiation factor eIF2α and the redistribution of cellular proteins from the nucleus to the cytoplasm...
February 8, 2018: Viruses
https://www.readbyqxmd.com/read/29415133/translation-initiation-of-alphavirus-mrna-reveals-new-insights-into-the-topology-of-the-48s-initiation-complex
#13
René Toribio, Irene Díaz-López, Jasminka Boskovic, Iván Ventoso
The topology and dynamics of the scanning ribosomal 43S pre-initiation complex (PIC) bound to mRNA and initiation factors (eIFs) are probably the least understood aspects of translation initiation in eukaryotes. Recently, we described a trapping mechanism in alphavirus that stalls the PIC during scanning of viral mRNA. Using this model, we were able to snapshot for the first time the eIF4A helicase bound to mRNA in a 48S initiation complex assembled in vitro. This interaction was only detected in the presence of the natural stem loop structure (DLP) located downstream from the AUG in viral mRNA that promoted stalling of the PIC, suggesting that DLP stability was enough to jam the helicase activity of eIF4A in a fraction of assembled 48S complexes...
February 5, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29397069/characterisation-of-the-biological-response-of-saccharomyces-cerevisiae-to-the-loss-of-an-allele-of-the-eukaryotic-initiation-factor-4a
#14
Veronica Venturi, Richard Little, Peter W Bircham, Juliana Rodigheri Brito, Paul H Atkinson, David R Maass, Paul H Teesdale-Spittle
The translation initiation machinery is emerging as an important target for therapeutic intervention, with potential in the treatment of cancer, viral infections, and muscle wasting. Amongst the targets for pharmacological control of translation initiation is the eukaryotic initiation factor 4A (eIF4A), an RNA helicase that is essential for cap-dependent translation initiation. We set out to explore the system-wide impact of a reduction of functional eIF4A. To this end, we investigated the effect of deletion of TIF1, one of the duplicate genes that produce eIF4A in yeast, through synthetic genetic array interactions and system-wide changes in GFP-tagged protein abundances...
February 19, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29381712/plant-growth-and-fertility-requires-functional-interactions-between-specific-pabp-and-eif4g-gene-family-members
#15
Daniel R Gallie
The initiation of protein synthesis requires the involvement of the eukaryotic translation initiation factor (eIF) 4G to promote assembly of the factors needed to recruit a 40S ribosomal subunit to an mRNA. Although many eukaryotes express two eIF4G isoforms that are highly similar, those in plants, referred to as eIF4G and eIFiso4G, are highly divergent in size, sequence, and domain organization. Species of the Brassicaceae and the Cleomaceae also express a divergent eIFiso4G isoform, referred to as eIFiso4G2, not found elsewhere in the plant kingdom...
2018: PloS One
https://www.readbyqxmd.com/read/29337852/reference-gene-selection-for-quantitative-real-time-reverse-transcriptase-pcr-in-annual-ryegrass-lolium-multiflorum-subjected-to-various-abiotic-stresses
#16
Qiuxu Liu, Xiao Qi, Haidong Yan, Linkai Huang, Gang Nie, Xinquan Zhang
To select the most stable reference genes in annual ryegrass ( Lolium multiflorum ), we studied annual ryegrass leaf tissues exposed to various abiotic stresses by qRT-PCR and selected 11 candidate reference genes, i.e., 18S rRNA, E2, GAPDH, eIF4A, HIS3, SAMDC, TBP-1, Unigene71, Unigene77, Unigene755, and Unigene14912. We then used GeNorm, NormFinder, and BestKeeper to analyze the expression stability of these 11 genes, and used RefFinder to comprehensively rank genes according to stability. Under different stress conditions, the most suitable reference genes for studies of leaf tissues of annual ryegrass were different...
January 16, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29288414/trypanosoma-brucei-eif4e2-cap-binding-protein-binds-a-homolog-of-the-histone-mrna-stem-loop-binding-protein
#17
Eden R Freire, Danielle M N Moura, Maria J R Bezerra, Camila C Xavier, Mariana C Morais-Sobral, Ajay A Vashisht, Antonio M Rezende, James A Wohlschlegel, Nancy R Sturm, Osvaldo P de Melo Neto, David A Campbell
Trypanosomatids are parasitic protozoans characterized by several unique structural and metabolic processes that include exquisite mechanisms associated with gene expression and regulation. During the initiation of protein synthesis, for instance, mRNA selection for translation seems to be mediated by different eIF4F-like complexes, which may play a significant role in parasite adaptation to different hosts. In eukaryotes, the heterotrimeric eIF4F complex (formed by eIF4E, eIF4G, and eIF4A) mediates mRNA recognition and ribosome binding and participates in various translation regulatory events...
December 29, 2017: Current Genetics
https://www.readbyqxmd.com/read/29258862/broad-spectrum-antiviral-activity-of-the-eif4a-inhibitor-silvestrol-against-corona-and-picornaviruses
#18
Christin Müller, Falk W Schulte, Kerstin Lange-Grünweller, Wiebke Obermann, Ramakanth Madhugiri, Stephan Pleschka, John Ziebuhr, Roland K Hartmann, Arnold Grünweller
Coronaviruses (CoV) and picornaviruses are plus-strand RNA viruses that use 5' cap-dependent and cap-independent strategies, respectively, for viral mRNA translation initiation. Here, we analyzed the effects of the plant compound silvestrol, a specific inhibitor of the DEAD-box RNA helicase eIF4A, on viral translation using a dual luciferase assay and virus-infected primary cells. Silvestrol was recently shown to have potent antiviral activity in Ebola virus-infected human macrophages. We found that silvestrol is also a potent inhibitor of cap-dependent viral mRNA translation in CoV-infected human embryonic lung fibroblast (MRC-5) cells...
February 2018: Antiviral Research
https://www.readbyqxmd.com/read/29258238/stress-granule-inducing-eukaryotic-translation-initiation-factor-4a-inhibitors-block-influenza-a-virus-replication
#19
Patrick D Slaine, Mariel Kleer, Nathan K Smith, Denys A Khaperskyy, Craig McCormick
Eukaryotic translation initiation factor 4A (eIF4A) is a helicase that facilitates assembly of the translation preinitiation complex by unwinding structured mRNA 5' untranslated regions. Pateamine A (PatA) and silvestrol are natural products that disrupt eIF4A function and arrest translation, thereby triggering the formation of cytoplasmic aggregates of stalled preinitiation complexes known as stress granules (SGs). Here we examined the effects of eIF4A inhibition by PatA and silvestrol on influenza A virus (IAV) protein synthesis and replication in cell culture...
December 18, 2017: Viruses
https://www.readbyqxmd.com/read/29222490/ran-translation-at-c9orf72-associated-repeat-expansions-is-selectively-enhanced-by-the-integrated-stress-response
#20
Katelyn M Green, M Rebecca Glineburg, Michael G Kearse, Brittany N Flores, Alexander E Linsalata, Stephen J Fedak, Aaron C Goldstrohm, Sami J Barmada, Peter K Todd
Repeat-associated non-AUG (RAN) translation allows for unconventional initiation at disease-causing repeat expansions. As RAN translation contributes to pathogenesis in multiple neurodegenerative disorders, determining its mechanistic underpinnings may inform therapeutic development. Here we analyze RAN translation at G4 C2 repeat expansions that cause C9orf72-associated amyotrophic lateral sclerosis and frontotemporal dementia (C9RAN) and at CGG repeats that cause fragile X-associated tremor/ataxia syndrome...
December 8, 2017: Nature Communications
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