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Cap-dependent translation

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https://www.readbyqxmd.com/read/28529622/ires-mediated-protein-translation-overcomes-suppression-by-the-p14arf-tumor-suppressor-protein
#1
Song Xi, Ming Zhao, Si Wang, Ling Ma, Shensen Wang, Xianling Cong, Ruth A Gjerset, Rebecca C Fitzgerald, Yinghui Huang
Internal ribosome entry sites (IRES elements) have attracted interest in cancer gene therapy because they can be used in the design of gene transfer vectors that provide bicistronic co-expression of two transgene products under the control of a single promoter. Unlike cellular translation of most mRNAs, a process that requires a post-translational 5' modification of the mRNA known as the cap structure, IRES-mediated translation is independent of the cap structure. The cellular conditions that may intervene to modulate IRES-mediated, cap-independent versus cap-dependent translation, however, remain poorly understood, although they could be critical to the choice of gene transfer vectors...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28518150/cycloheximide-promotes-paraptosis-induced-by-inhibition-of-cyclophilins-in-glioblastoma-multiforme
#2
Lin Wang, Justin H Gundelach, Richard J Bram
Cancer is the second leading cause of death worldwide. Current treatment strategies based on multi-agent chemotherapy and/or radiation regimens have improved overall survival in some cases. However, resistance to apoptosis often develops in cancer cells, and its occurrence is thought to contribute to treatment failure. Non-apoptotic cell death mechanisms have become of great interest, therefore, in hopes that they would bypass tumor cell resistance. Glioblastoma multiforme (GBM), a grade IV astrocytic tumor is the most frequent brain tumor in adults, and has a high rate of mortality...
May 18, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28507282/p53-suppresses-ribonucleotide-reductase-via-inhibiting-mtorc1
#3
Zhengfu He, Xing Hu, Weijin Liu, Adrienne Dorrance, Ramiro Garzon, Peter J Houghton, Changxian Shen
Balanced deoxyribonucleotides pools are essential for cell survival and genome stability. Ribonucleotide reductase is the rate-limiting enzyme for the production of deoxyribonucleotides. We report here that p53 suppresses ribonucleotide reductase subunit 1 (RRM1) and 2 (RRM2) via inhibiting mammalian target of rapamycin complex 1 (mTORC1). In vitro, cancer cell lines and mouse embryonic fibroblast cells were treated with different concentrations of pharmacological inhibitors for different times. In vivo, rhabdomyosarcoma Rh30 cell tumor-bearing mice were treated with rapamycin or AZD8055...
April 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28468879/regulation-of-tacaribe-mammarenavirus-translation-positive-5-and-negative-3-elements-and-role-of-key-cellular-factors
#4
Sabrina Foscaldi, Alejandra D'Antuono, María Gabriela Noval, Gonzalo de Prat Gay, Luis Scolaro, Nora Lopez
Mammarenaviruses are enveloped viruses with a bisegmented negative-stranded RNA genome that encodes the nucleocapsid protein (NP), the envelope glycoprotein precursor (GPC), the RNA polymerase (L), and a RING matrix protein (Z). Viral proteins are synthesized from subgenomic messenger RNAs bearing a capped 5' untranslated region (UTR), and lacking 3' poly(A) tail. We analyzed the translation strategy of Tacaribe virus (TCRV), a prototype of the New World mammarenaviruses. A virus-like transcript that carries a reporter gene in place of the NP open-reading frame as well as transcripts bearing modified 5' and/or 3' UTRs were evaluated in a cell-based translation assay...
May 3, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28452293/separation-of-foot-and-mouth-disease-virus-leader-protein-activities-identification-of-mutants-that-retain-efficient-self-processing-activity-but-poorly-induce-eif4g-cleavage
#5
Su Hua Guan, Graham J Belsham
Foot-and-mouth disease virus is a picornavirus and its RNA genome encodes a large polyprotein. The N-terminal part of this polyprotein is the leader protein, a cysteine protease, termed Lpro. The virus causes the rapid inhibition of host cell cap-dependent protein synthesis within infected cells. This results from the Lpro-dependent cleavage of the cellular translation initiation factor eIF4G. Lpro also releases itself from the virus capsid precursor by cleaving the L/P1 junction. Using site-directed mutagenesis of the Lpro coding sequence, we have investigated the role of 51 separate amino acid residues in the functions of this protein...
April 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28438065/reduced-expression-of-eukaryotic-translation-initiation-factor-3-subunit-e-and-its-possible-involvement-in-the-epithelial-mesenchymal-transition-in-endometriosis
#6
Xianjun Cai, Minhong Shen, Xishi Liu, Sun-Wei Guo
Epithelial-mesenchymal transition (EMT) is now well documented to be involved in the development of endometriosis through the promotion of invasion and fibrogenesis. To date, several factors have been reported to be involved in EMT in endometriosis. The eukaryotic translation initiation factor 3 subunit e (eIF3e) protein is a component of the multisubunit eIF3 complex essential for cap-dependent translation initiation. The aim of this study was to investigate whether eIF3e is involved in EMT in endometriosis...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28428795/non-canonical-translation-in-plant-rna-viruses
#7
REVIEW
Manuel Miras, W Allen Miller, Verónica Truniger, Miguel A Aranda
Viral protein synthesis is completely dependent upon the host cell's translational machinery. Canonical translation of host mRNAs depends on structural elements such as the 5' cap structure and/or the 3' poly(A) tail of the mRNAs. Although many viral mRNAs are devoid of one or both of these structures, they can still translate efficiently using non-canonical mechanisms. Here, we review the tools utilized by positive-sense single-stranded (+ss) RNA plant viruses to initiate non-canonical translation, focusing on cis-acting sequences present in viral mRNAs...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28417568/cisplatin-resistant-cancer-cells-are-sensitive-to-aurora-kinase-a-inhibition-by-alisertib
#8
Lihong Wang, Janet Arras, Ahmed Katsha, Saif Hamdan, Abbes Belkhiri, Jeffrey Ecsedy, Wael El-Rifai
De novo and acquired resistance to platinum therapy such as cisplatin (CDDP) is a clinical challenge in gastric cancer treatment. Aberrant expression and activation of Aurora kinase A (AURKA) and eukaryotic translation initiation factor 4E (eIF4E) are detected in several cancer types. Herein, we investigated the role of AURKA in CDDP resistance in gastric cancer. Western blot analysis demonstrated overexpression of AURKA and phosphorylation of eIF4E in acquired and de novo CDDP-resistant gastric cancer models...
April 18, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28408475/regulation-of-human-immunodeficiency-virus-type-1-hiv-1-mrna-translation
#9
REVIEW
Laura Hidalgo, Chad M Swanson
Human immunodeficiency virus type 1 (HIV-1) mRNA translation is a complex process that uses the host translation machinery to synthesise viral proteins. Several mechanisms for HIV-1 mRNA translation initiation have been proposed including (1) cap-dependent, eIF4E-dependent, (2) cap-dependent, cap-binding complex-dependent, (3) internal ribosome entry sites, and (4) ribosome shunting. While these mechanisms promote HIV-1 mRNA translation in the context of in vitro systems and subgenomic constructs, there are substantial knowledge gaps in understanding how they regulate viral protein production in the context of full-length virus infection...
April 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28377580/the-5-utr-in-human-adenoviruses-leader-diversity-in-late-gene-expression
#10
Mirja Ramke, Jeong Yoon Lee, David W Dyer, Donald Seto, Jaya Rajaiya, James Chodosh
Human adenoviruses (HAdVs) shut down host cellular cap-dependent mRNA translation while initiating the translation of viral late mRNAs in a cap-independent manner. HAdV 5' untranslated regions (5'UTRs) are crucial for cap-independent initiation, and influence mRNA localization and stability. However, HAdV translational regulation remains relatively uncharacterized. The HAdV tripartite leader (TPL), composed of three introns (TPL 1-3), is critical to the translation of HAdV late mRNA. Herein, we annotated and analyzed 72 HAdV genotypes for the HAdV TPL and another previously described leader, the i-leader...
April 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28350134/microrna-455-3p-functions-as-a-tumor-suppressor-by-targeting-eif4e-in-prostate-cancer
#11
Yongxiang Zhao, Mingyu Yan, Ye Yun, Jianguo Zhang, Ruimin Zhang, Yan Li, Xiangming Wu, Qiang Liu, Wei Miao, Haishan Jiang
MicroRNAs (miRNAs) are strongly implicated in various cancers, including prostate cancer. Recently, microRNA-455-3p (miR-455-3p) has been shown to be aberrantly expressed in many tumor tissues, but its functions in tumorigenesis remain unknown. In this study, we investigated the role of miR-455-3p in prostate cancer. We found that miR-455-3p is markedly downregulated in prostate cancer cell lines and clinical tumor specimens. Gain-of-function and loss-of-function studies showed that miR-455-3p promotes prostate cancer cell growth both in vitro and in vivo...
April 2017: Oncology Reports
https://www.readbyqxmd.com/read/28344082/circ-znf609-is-a-circular-rna-that-can-be-translated-and-functions-in-myogenesis
#12
Ivano Legnini, Gaia Di Timoteo, Francesca Rossi, Mariangela Morlando, Francesca Briganti, Olga Sthandier, Alessandro Fatica, Tiziana Santini, Adrian Andronache, Mark Wade, Pietro Laneve, Nikolaus Rajewsky, Irene Bozzoni
Circular RNAs (circRNAs) constitute a family of transcripts with unique structures and still largely unknown functions. Their biogenesis, which proceeds via a back-splicing reaction, is fairly well characterized, whereas their role in the modulation of physiologically relevant processes is still unclear. Here we performed expression profiling of circRNAs during in vitro differentiation of murine and human myoblasts, and we identified conserved species regulated in myogenesis and altered in Duchenne muscular dystrophy...
April 6, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28338950/nonreplicative-rna-recombination-of-an-animal-plus-strand-rna-virus-in-the-absence-of-efficient-translation-of-viral-proteins
#13
Maximiliane Kleine Büning, Denise Meyer, Sophia Austermann-Busch, Gleyder Roman-Sosa, Tillmann Rümenapf, Paul Becher
RNA recombination is a major driving force for the evolution of RNA viruses and is significantly implicated in the adaptation of viruses to new hosts, changes of virulence, as well as in the emergence of new viruses including drug-resistant and escape mutants. However, the molecular details of recombination in animal RNA viruses are only poorly understood. In order to determine whether viral RNA recombination depends on translation of viral proteins, a nonreplicative recombination system was established which is based on cotransfection of cells with synthetic bovine viral diarrhea virus (family Flaviviridae) RNA genome fragments either lacking the internal ribosome entry site required for cap-independent translation or lacking almost the complete polyprotein coding region...
April 1, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/28325843/a-biochemical-framework-for-eif4e-dependent-mrna-export-and-nuclear-re-cycling-of-the-export-machinery
#14
Laurent Volpon, Biljana Culjkovic-Kraljacic, Hye Seon Sohn, Alexis Blanchett-Cohen, Michael J Osborne, Katherine L B Borden
The eukaryotic translation initiation factor eIF4E acts in the nuclear export and translation of a subset of mRNAs. Both of these functions contribute to its oncogenic potential. While the biochemical mechanisms that underlie translation are relatively well understood, the molecular basis for eIF4E's role in mRNA export remains largely unexplored. To date over 3000 transcripts, many encoding oncoproteins, were identified as potential nuclear eIF4E export targets. These target RNAs typically contain a ~50 nucleotide eIF4E sensitivity element (4ESE) in the 3' UTR and a 7-methylguanosine cap on the 5' end...
March 21, 2017: RNA
https://www.readbyqxmd.com/read/28323169/isolation-and-characterization-of-human-capg-expressed-and-post-translationally-modified-in-pichia-pastoris
#15
Agnes Papala, Marc Sylvester, Nadine Dyballa-Rukes, Sabine Metzger, Jochen D'Haese
CapG is an actin-binding protein, which is overexpressed in a variety of tumors, i.e. breast, ovarian, pancreatic and lung carcinoma. We successfully expressed human CapG in the wild type strain X-33 of the methylotrophic yeast Pichia pastoris (P. pastoris), which does not express endogenous CapG, in order to characterize this protein in more detail. After mechanical cell lysis, debris was centrifuged and the soluble protein was precipitated with ammonium sulfate. This protein pellet was dialyzed and used for CapG purification...
March 18, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28322282/maternal-immune-activation-dysregulation-of-the-fetal-brain-transcriptome-and-relevance-to-the-pathophysiology-of-autism-spectrum-disorder
#16
M V Lombardo, H M Moon, J Su, T D Palmer, E Courchesne, T Pramparo
Maternal immune activation (MIA) via infection during pregnancy is known to increase risk for autism spectrum disorder (ASD). However, it is unclear how MIA disrupts fetal brain gene expression in ways that may explain this increased risk. Here we examine how MIA dysregulates rat fetal brain gene expression (at a time point analogous to the end of the first trimester of human gestation) in ways relevant to ASD-associated pathophysiology. MIA downregulates expression of ASD-associated genes, with the largest enrichments in genes known to harbor rare highly penetrant mutations...
March 21, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28272965/regulation-of-4e-bp1-activity-in-the-mammalian-oocyte
#17
Denisa Jansova, Marketa Koncicka, Anna Tetkova, Renata Cerna, Radek Malik, Edgar Del Llano, Michal Kubelka, Andrej Susor
Fully grown mammalian oocytes utilize transcripts synthetized and stored during earlier development. RNA localization followed by a local translation is a mechanism responsible for the regulation of spatial and temporal gene expression. Here we show that the mouse oocyte contains 3 forms of cap-dependent translational repressor expressed on the mRNA level: 4E-BP1, 4E-BP2 and 4E-BP3. However, only 4E-BP1 is present as a protein in oocytes, it becomes inactivated by phosphorylation after nuclear envelope breakdown and as such it promotes cap-dependent translation after NEBD...
March 8, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28251928/structure-of-human-ifit1-with-capped-rna-reveals-adaptable-mrna-binding-and-mechanisms-for-sensing-n1-and-n2-ribose-2-o-methylations
#18
Yazan M Abbas, Beatrice Theres Laudenbach, Saúl Martínez-Montero, Regina Cencic, Matthias Habjan, Andreas Pichlmair, Masad J Damha, Jerry Pelletier, Bhushan Nagar
IFIT1 (IFN-induced protein with tetratricopeptide repeats-1) is an effector of the host innate immune antiviral response that prevents propagation of virus infection by selectively inhibiting translation of viral mRNA. It relies on its ability to compete with the translation initiation factor eIF4F to specifically recognize foreign capped mRNAs, while remaining inactive against host mRNAs marked by ribose 2'-O methylation at the first cap-proximal nucleotide (N1). We report here several crystal structures of RNA-bound human IFIT1, including a 1...
March 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28242456/the-proangiogenic-potential-of-a-novel-calcium-releasing-composite-biomaterial-orthotopic-in-vivo-evaluation
#19
Hugo Oliveira, Sylvain Catros, Oscar Castano, Sylvie Rey, Robin Siadous, Douglas Clift, Joan Marti-Munoz, Marc Batista, Reine Bareille, Josep Planell, Elisabeth Engel, Joëlle Amédée
Insufficient angiogenesis remains a major hurdle in current bone tissue engineering strategies. An extensive body of work has focused on the use of angiogenic factors or endothelial progenitor cells. However, these approaches are inherently complex, in terms of regulatory and methodologic implementation, and present a high cost. We have recently demonstrate the potential of electrospun poly(lactic acid) (PLA) fiber-based membranes, containing calcium phosphate (CaP) ormoglass particles, to elicit angiogenesis in vivo, in a subcutaneous model in mice...
February 24, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28242053/regulation-mechanisms-of-viral-ires-driven-translation
#20
REVIEW
Kuo-Ming Lee, Chi-Jene Chen, Shin-Ru Shih
Internal ribosome entry sites (IRESs) can be found in the mRNA of many viruses as well as in cellular genes involved in the stress response, cell cycle, and apoptosis. IRES-mediated translation can occur when dominant cap-dependent translation is inhibited, and viruses can take advantage of this to subvert host translation machinery. In this review, we focus on the four major types of IRES identified in RNA viruses, and outline their distinct structural properties and requirements of translational factors. We further discuss auxiliary host factors known as IRES trans-acting factors (ITAFs), which are involved in the modulation of optimal IRES activity...
February 24, 2017: Trends in Microbiology
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