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regulated IRE-1 dependent

Jhee Hong Koh, Lei Wang, Caroline Beaudoin-Chabot, Guillaume Thibault
Metabolic disorders such as nonalcoholic fatty liver disease (NAFLD) are emerging epidemics that affect the global population. One facet of these disorders is attributed to the disturbance of membrane lipid composition. Perturbation of endoplasmic reticulum (ER) homeostasis through alteration in membrane phospholipids activates the unfolded protein response (UPR) and causes dramatic transcriptional and translational changes in the cell. To restore cellular homeostasis, the three highly conserved UPR transducers ATF6, IRE1, and PERK mediate adaptive responses upon ER stress...
October 17, 2018: Journal of Cell Science
Jun-Hao Chen, Rui-Hua Zhang, Shao-Li Lin, Peng-Fei Li, Jing-Jing Lan, Sha-Sha Song, Ji-Ming Gao, Yu Wang, Zhi-Jing Xie, Fu-Chang Li, Shi-Jin Jiang
The duck hepatitis A virus type 1 (DHAV-1) is a member of Picornaviridae family, the genome of the virus contains a 5' untranslated region (5' UTR), a large open reading frame that encodes a polyprotein precursor and a 3' UTR followed by a poly(A) tail. The translation initiation of virus proteins depends on the internal ribosome-entry site (IRES) element within the 5' UTR. So far, little information is known about the role of the 3' UTR and poly(A) tail during the virus proliferation. In this study, the function of the 3' UTR and poly(A) tail of DHAV-1 in viral replication and IRES-mediated translation was investigated...
2018: Frontiers in Microbiology
Kazuhiro Iwai
Because of essentiality and toxicity of iron in our body, iron metabolism is tightly regulated in cells. In mammalian cells, iron regulatory protein 1 and 2 (IRP1 and IRP2) are the central regulators of cellular iron metabolism. IRPs regulate iron metabolism by interacting with the RNA stem-loop structures, iron-responsive elements (IREs), found on the transcripts encoding proteins involved in iron metabolism only in iron depleted condition. It is also well-known that the ubiquitin system plays central roles in cellular iron regulation because both IRPs having the IRE binding activity are recognized and ubiquitinated by the SCFFBXL5 ubiquitin ligase in condition of iron-replete...
September 12, 2018: Free Radical Biology & Medicine
C Joaquín Cáceres, Jenniffer Angulo, Fernando Lowy, Nataly Contreras, Beth Walters, Eduardo Olivares, Delphine Allouche, Anne Merviel, Karla Pino, Bruno Sargueil, Sunnie R Thompson, Marcelo López-Lastra
Human T-cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia (ATL). The HTLV-1 basic leucine zipper protein (HBZ) is expressed in all cases of ATL and is directly associated with virus pathogenicity. The two isoforms of the HBZ protein are synthesized from antisense messenger RNAs (mRNAs) that are either spliced (sHBZ) or unspliced (usHBZ) versions of the HBZ transcript. The sHBZ and usHBZ mRNAs have entirely different 5'untranslated regions (5'UTR) and are differentially expressed in cells, with the sHBZ protein being more abundant...
September 12, 2018: Nucleic Acids Research
Yang Yang, Chenfeng Wang, Kailiang Zhao, Guang Zhang, Decai Wang, Yide Mei
The tumor suppressor p53 plays a pivotal role in the protection against cancer. Increasing evidence suggests that long noncoding RNA (lncRNA) plays an important role in the regulation of the p53 pathway, however, the detailed mechanisms remain to be further elucidated. In this study, we report a new p53-inducible lncRNA that we termed TRMP (TP53-regulated modulator of p27). As a direct transcriptional target of p53, TRMP plays an unexpected pro-survival function. Knockdown of TRMP inhibits cell proliferation by inducing a G1 cell cycle arrest...
August 30, 2018: Cell Death & Disease
Vivek Venkataramani, Thorsten R Doeppner, Desiree Willkommen, Catherine M Cahill, Yongjuan Xin, Guilin Ye, Yanyan Liu, Adam Southon, Allegra Aron, Ho Yu Au-Yeung, Xudong Huang, Debomoy K Lahiri, Fudi Wang, Ashley I Bush, Gerald G Wulf, Philipp Ströbel, Bernhard Michalke, Jack T Rogers
For more than 150 years it is known that occupational overexposure of manganese (Mn) causes movement disorders resembling Parkinson's disease (PD) and PD-like syndromes. However, the mechanisms of Mn toxicity are still poorly understood. Here, we demonstrate that Mn dose- and time-dependently blocks the protein translation of amyloid precursor protein (APP) and heavy-chain Ferritin (H-Ferritin), both iron homeostatic proteins with neuroprotective features. APP and H-Ferritin are post-transcriptionally regulated by iron responsive proteins (IRPs), which bind to homologous iron responsive elements (IREs) located in the 5'-untranslated regions (5'-UTRs) within their mRNA transcripts...
August 27, 2018: Journal of Neurochemistry
Carlo Mangia, Alice Vismarra, Marco Genchi, Sara Epis, Claudio Bandi, Giulio Grandi, Lesley Bell-Sakyi, Domenico Otranto, Benedetta Passeri, Laura Kramer
BACKGROUND: Over-expression of ATP-binding cassette (ABC) transporter proteins has been implicated in resistance of ticks to acaricides. Tick cell lines are useful for investigating resistance mechanisms, as development of an in vitro model for the study of acaricide resistance would contribute to improving knowledge of the molecular basis behind drug processing and exclusion in ticks. In the present study, cultures of the Ixodes ricinus-derived cell line IRE/CTVM19 were treated with the acaricides amitraz, permethrin or fipronil to determine modulation of ABC transporter gene expression...
July 31, 2018: Parasites & Vectors
Megan A Peppenelli, Michael J Miller, Aaron M Altman, Olesea Cojohari, Gary C Chan
Primary peripheral blood monocytes are responsible for the hematogenous dissemination of human cytomegalovirus (HCMV) following a primary infection. In order to facilitate viral spread, HCMV extends the naturally short 48-h lifespan of monocytes by stimulating a non-canonical activation of Akt during viral entry, which leads to the increased expression of a specific subset of antiapoptotic proteins. In this study, global analysis of the Akt signaling network showed HCMV induced a more robust activation of the entire network when compared to normal myeloid growth factors...
October 2018: Antiviral Research
Shuang-Shuang Yang, Jigui Wang, Zhaoda Li, Shangjin Cui, Weiquan Liu
Mink enteritis virus (MEV), as a parvovirus, is among the smallest of the animal DNA viruses. The limited genome leads to multifunctional sequences and complex gene expression regulation. Here, we show that the expression of viral capsid protein 2 (VP2) of MEV requires its 5' untranslated regions (5' UTR) which promote VP2 gene expression at both transcriptional and translational levels. The expression of VP2 was inhibited in several common eukaryotic expression vectors. Our data showed that the 5' UTR of VP2 enhanced capsid gene transcription but not increased stability or promotes nucleocytoplasmic export of VP2 mRNA...
September 15, 2018: Journal of Virology
Ram Kumar, Nitin Khandelwal, Riyesh Thachamvally, Bhupendra Nath Tripathi, Sanjay Barua, Sudhir Kumar Kashyap, Sunil Maherchandani, Naveen Kumar
Viruses are obligate intracellular parasites; they heavily depend on the host cell machinery to effectively replicate and produce new progeny virus particles. Following viral infection, diverse cell signaling pathways are initiated by the cells, with the major goal of establishing an antiviral state. However, viruses have been shown to exploit cellular signaling pathways for their own effective replication. Genome-wide siRNA screens have also identified numerous host factors that either support (proviral) or inhibit (antiviral) virus replication...
July 15, 2018: Virus Research
Fabrizio Damiano, Mariangela Testini, Romina Tocci, Gabriele V Gnoni, Luisa Siculella
Acetyl-CoA carboxylase 1 (ACC1) is a cytosolic enzyme catalyzing the rate limiting step in de novo fatty acid biosynthesis. There is mounting evidence showing that ACC1 is susceptible to dysregulation and that it is over-expressed in liver diseases associated with lipid accumulation and in several cancers. In the present study, ACC1 regulation at the translational level is reported. Using several experimental approaches, the presence of an internal ribosome entry site (IRES) has been established in the 5' untranslated region (5' UTR) of the ACC1 mRNA...
April 2018: Biochimica et biophysica acta. Molecular and cell biology of lipids
Yanling Yan, Conghui Li, Binlian Sun, Rongge Yang
Hepatitis C virus (HCV) is a worldwide threaten to human health with a high ratio of chronic infections. Recently, we found that Vpr-mediated regulation of HCV replication depends on the host protein DDB1-Cul4 associate factor 1 (DCAF1), implying that DCAF1 might be involved in the replication of HCV. In this study, we demonstrated that DCAF1 knockdown reduced HCV replication both in the infectious (JFH1) and replicon (Con1) systems. Further investigation showed a negative regulation of HCV internal ribosome entry site (IRES)-mediated translation by DCAF1...
April 2018: Archives of Virology
Lin Li, Jiahui Cui, Zi Liu, Xuejiao Zhou, Zengqiang Li, Yang Yu, Yuanyuan Jia, Daiying Zuo, Yingliang Wu
Silver nanoparticles (AgNPs) have many medical and commercial applications, but their effects on human health are poorly understood. The aim of this study was to assess the effect of AgNPs on the human neuroblastoma cell line SH-SY5Y and to explore their potential mechanisms of action. We found that AgNPs decreased SH-SY5Y cell viability in a dose- and time-dependent manner. Exposure to AgNPs activated endoplasmic reticulum (ER) stress, as reflected by upregulated expression of glucose-regulated protein 78 (GRP78), phosphorylated PKR-like endoplasmic reticulum kinase (p-PERK), phosphorylated eukaryotic translation initiation factor 2α (p-eIF2α), C/EBP homology protein (CHOP), spliced X-box binding protein-1 (XBP1), and phosphorylated inositol-requiring enzyme (p-IRE), all of which are involved in the cellular unfolded protein response...
March 15, 2018: Toxicology Letters
Xiao-Ming Li, Xiao-Jie Zhang, Miao-Xian Dong
Endoplasmic reticulum stress (ERS) and mitochondrial dysfunctions are thought to be involved in the dopaminergic neuronal death in Parkinson's disease (PD). In this study, we found that isorhynchophylline (IRN) significantly attenuated 1-methyl-4-phenylpyridinium (MPP+ )-induced apoptotic cell death and oxidative stress in PC12 cells. IRN markedly reduced MPP+ -induced-ERS responses, indicative of inositol-requiring enzyme 1 (IRE1) phosphorylation and caspase-12 activation. Furthermore, IRN inhibits MPP+ -triggered apoptosis signal-regulating kinase 1 (ASK1)/c-Jun N-terminal Kinase (JNK) signaling-mediated mitochondria-dependent apoptosis pathway...
December 2017: Neuromolecular Medicine
Alfonso Galan, Gloria Lozano, David Piñeiro, Encarnacion Martinez-Salas
RNA-protein interactions play a pivotal role in the function of picornavirus internal ribosome entry site (IRES) elements. Here we analysed the impact of Ras GTPase SH3 domain binding protein 1 (G3BP1) in the IRES activity of foot-and-mouth disease virus (FMDV). We found that G3BP1 interacts directly with three distinct sequences of the IRES element using RNA electrophoretic mobility-shift assays. Analysis of the interaction with domain 5 indicated that the G3BP1 binding-site is placed at the single-stranded region although it allows large sequence heterogeneity and the hairpin located upstream of this region enhances retarded complex formation...
October 2017: FEBS Journal
Anna Milczarek, Rafał R Starzyński, Agnieszka Styś, Aneta Jończy, Robert Staroń, Agnieszka Grzelak, Paweł Lipiński
Iron regulatory protein 1 (IRP1) is a cytosolic bifunctional [4Fe-4S] protein which exhibits aconitase activity or binds iron responsive elements (IREs) in untranslated regions of specific mRNA encoding proteins involved in cellular iron metabolism. Superoxide radical (O2.-) converts IRP1 from a [4Fe-4S] aconitase to a [3Fe-4S] "null" form possessing neither aconitase nor trans-regulatory activity. Genetic ablation of superoxide dismutase 1 (SOD1), an antioxidant enzyme that acts to reduce O2.- concentration, revealed a new O2...
2017: PloS One
Yehuda Salzberg, Andrew J Coleman, Kevin Celestrin, Moran Cohen-Berkman, Thomas Biederer, Sivan Henis-Korenblit, Hannes E Bülow
Neurons receive excitatory or sensory inputs through their dendrites, which often branch extensively to form unique neuron-specific structures. How neurons regulate the formation of their particular arbor is only partially understood. In genetic screens using the multidendritic arbor of PVD somatosensory neurons in the nematode Caenorhabditis elegans, we identified a mutation in the ER stress sensor IRE-1/Ire1 (inositol requiring enzyme 1) as crucial for proper PVD dendrite arborization in vivo. We further found that regulation of dendrite growth in cultured rat hippocampal neurons depends on Ire1 function, showing an evolutionarily conserved role for IRE-1/Ire1 in dendrite patterning...
January 2017: PLoS Genetics
Yang Han, Lvyin Wang, Jin Cui, Yu Song, Zhen Luo, Junbo Chen, Ying Xiong, Qi Zhang, Fang Liu, Wenzhe Ho, Yingle Liu, Kailang Wu, Jianguo Wu
Enterovirus 71 (EV71) possesses a single-stranded positive RNA genome that contains a single open reading frame (ORF) flanked by a 5' untranslated region (5'UTR) and a polyadenylated 3'UTR. Here, we demonstrated that EV71 activates the production of silent mating type information regulation 2 homolog 1 (SIRT1), a histone deacetylase (HDAC). EV71 further stimulates SIRT1 sumoylation and deacetylase activity, and enhances SIRT1 translocation from the nucleus to the cytoplasm. More interestingly, activated SIRT1 subsequently binds with the EV71 3Dpol protein (a viral RNA-dependent RNA polymerase, RdRp) to repress the acetylation and RdRp activity of 3Dpol , resulting in the attenuation of viral genome replication...
December 15, 2016: Journal of Cell Science
Jacey H Ma, Joshua J Wang, Junhua Li, Bruce A Pfeffer, Yiming Zhong, Sarah X Zhang
Purpose: The retinal pigment epithelium (RPE) tight junctions play a pivotal role in maintaining the homeostatic environment of the neural retina. Herein, we investigated the role of X-box binding protein 1 (XBP1), an endoplasmic reticulum (ER) stress-responsive transcription factor, in regulation of RPE tight junctions. Methods: Human RPE cell line (ARPE-19) and primary primate RPE cells were used for in vitro experiments and RPE-specific XBP1 knockout (KO) mice were used for in vivo study...
October 1, 2016: Investigative Ophthalmology & Visual Science
Florence Bonnet-Magnaval, Céline Philippe, Loïc Van Den Berghe, Hervé Prats, Christian Touriol, Eric Lacazette
Under physiological stress conditions the cell protects itself through a global blockade on cap-dependent translation of mRNA. This allows cap-independent mechanisms such as internal ribosome entry site (IRES)-mediated translation to take over and initiate the translation of a specific pool of mRNAs that encode proteins involved in protecting the cell from stress. Staufen 1 (Stau1) is an RNA-binding protein that has been previously implicated in the regulation of stress granule formation and therefore could play a key role in protecting the cell against stress stimuli such as oxidative and endoplasmic reticulum (ER) stress...
October 14, 2016: Biochemical and Biophysical Research Communications
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