Review
Biochemistry & Molecular Biology
Rita Marques, Rafaela Lacerda, Luisa Romao
Summary: RNA-based therapies targeting IRESs and ITAFs have shown potential benefits in various conditions. IRES-mediated translation is an alternative mechanism that helps maintain protein synthesis and is involved in stress response and disease development. The relationship between IRESs, ITAFs, tumorigenesis, and therapy resistance has been studied, providing new therapeutic targets and approaches. In addition, dysregulation of IRES-dependent translation initiation is also associated with neurological and cardiovascular diseases, muscular atrophies, and other syndromes.
Review
Virology
Brenda Lopez-Ulloa, Yazmin Fuentes, Magdalena S. Pizarro-Ortega, Marcelo Lopez-Lastra
Summary: In this review, we discuss vRNA IRES-mediated translation initiation, highlighting the role of RNA-binding proteins (RBPs), other than the canonical translation initiation factors, in regulating their activity.
Article
Virology
Mathew P. Kirby, Ciara Stevenson, Liam J. Worrall, Yihang Chen, Christina Young, Jisoo Youm, Natalie C. J. Strynadka, Douglas W. Allan, Eric Jan
Summary: Viruses rely on internal ribosome entry sites to utilize the host cell machinery for viral protein expression. Mutations in the hinge region of dicistrovirus IRES revealed its significant role in viral translation.
JOURNAL OF VIROLOGY
(2022)
Article
Virology
Xinying Wang, Marli Vlok, Stephane Flibotte, Eric Jan
Summary: The study explores a novel viral translational mechanism, uncovering the IGR IRES sequence from ancient Northwest territories cripavirus dating back 700 years. The research demonstrates that aNCV IRES can bind to ribosomes and drive translation, supporting the historical significance of this viral translational mechanism.
Article
Virology
Leandro Fernandez-Garcia, Jenniffer Angulo, Hade Ramos, Aldo Barrera, Karla Pino, Jorge Vera-Otarola, Marcelo Lopez-Lastra
Summary: The DENV IRES enables viral protein synthesis under conditions that suppress canonical translation initiation, with resistance to eIF4G cleavage and enhanced activity in HEK 293T cells expressing Human rhinovirus 2A protease. This study characterizes the mechanism dependent on an internal ribosome entry site (IRES) for DENV mRNA translation initiation both in vitro and in cells.
JOURNAL OF VIROLOGY
(2021)
Article
Immunology
Guan-Hong Wu, Kuo-Ming Lee, Chia-Yu Kao, Shin-Ru Shih
Summary: The role of the internal ribosome entry site (IRES) in determining the neurovirulence of enteroviruses EV-A71 and CV-A16 was characterized using an oral inoculation model. Replacing EV-A71 IRES with CV-A16 abolished neuropathological phenotypes, indicating that IRES determines the neurotropic potential of these viruses. Tissue-specific replication can be reflected in cell-based characterization.
MICROBES AND INFECTION
(2023)
Article
Biochemistry & Molecular Biology
Guowei Geng, Chengming Yu, Xuefeng Yuan
Summary: This study found that the IRES activity of RNA2 in wheat yellow mosaic virus varies. Through analysis of RNA structure and mutagenesis, it was found that certain structural elements in the LYJN isolate synergistically ensure higher IRES activity. Additionally, both the HC and LYJN isolates have conserved structural elements that ensure basic IRES activity. This study reveals a novel evolution pattern of IRES, regulating IRES activity by altering the number of eIF4E-binding sites.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2024)
Article
Microbiology
Yu-Siang Su, Lih-Hwa Hwang, Chi-Ju Chen
Summary: The study demonstrated the integral role of HSPA6 in EV-A71 infection as a positive regulator, showcasing its impact on viral protein production and virion assembly, specifically through the regulation of IRES-mediated translation.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Evan M. Zhao, Angelo S. Mao, Helena de Puig, Kehan Zhang, Nathaniel D. Tippens, Xiao Tan, F. Ann Ran, Isaac Han, Peter Q. Nguyen, Emma J. Chory, Tiffany Y. Hua, Pradeep Ramesh, David B. Thompson, Crystal Yuri Oh, Eric S. Zigon, Max A. English, James J. Collins
Summary: The use of eukaryotic toehold switches (eToeholds) allows for efficient induction of gene translation in eukaryotic cells, capable of distinguishing the presence of RNA transcripts under various circumstances. Through optimization of RNA annealing, up to 16-fold induction of transgene expression was achieved.
NATURE BIOTECHNOLOGY
(2022)
Article
Virology
Jenniffer Angulo, C. Joaquin Caceres, Nataly Contreras, Leandro Fernandez-Garcia, Nathalie Chamond, Melissa Ameur, Bruno Sargueil, Marcelo Lopez-Lastra
Summary: Translation initiation of HCV mRNA depends on an IRES, which is stimulated by PTB1 and PTB4, but not PTB2. In HuH-7 cells, PTB1 promotes HCV IRES-mediated initiation more strongly than PTB4, while in HEK293T cells, PTB1 and PTB4 stimulate HCV IRES activity to similar levels. Mutations in RRM domains of PTB1 and PTB4 affect their ability to promote HCV IRES activity.
Article
Biochemistry & Molecular Biology
Devadatta Gosavi, Iwona Wower, Irene K. Beckmann, Ivo L. Hofacker, Jacek Wower, Michael T. Wolfinger, Joanna Sztuba-Solinska
Summary: This study investigated the secondary and tertiary structures of BVDV IRES RNA using a combination of SHAPE-MaP and in silico modelling. The results revealed a modular architecture composed of three distinct structural domains and the formation of an H-type pseudoknot. Computational modelling provided a detailed picture of the tertiary structure and helix arrangement of BVDV IRES, and also showed that the pseudoknot is evolutionarily conserved among many Pestivirus species.
Article
Biochemistry & Molecular Biology
Nicholas K. Clark, Meghan T. Harris, William B. Dahl, Zachary Knotts, Michael T. Marr II
Summary: IRES-mediated translation initiation requires a different set of factors compared to canonical cap-dependent translation. Cellular IRES mechanisms may resemble viral type III IRESes, allowing them to function with limited initiation factors under stress conditions.
MOLECULAR AND CELLULAR BIOLOGY
(2023)
Article
Microbiology
Shiv Kumar, Rohit Verma, Sandhini Saha, Ashish Kumar Agrahari, Shivangi Shukla, Oinam Ningthemmani Singh, Umang Berry, Tushar Kanti Maiti, Shailendra Asthana, C. T. Ranjith-Kumar, Milan Surjit
Summary: Multiple processes exist in a cell to ensure continuous production of essential proteins through different translation processes. Viruses have evolved strategies to use the host translation machinery for their protein synthesis. This study identifies the RNA-protein interactome of the HEV IRESl element and demonstrates the roles of ribosomal protein RPL5 and RNA helicase A (DHX9) in mediating HEV IRESl activity, establishing it as a bona fide internal translation initiation site.
MICROBIOLOGY SPECTRUM
(2023)
Article
Medicine, Research & Experimental
Hui Li, Yuhang Chen, Junshi Zhang, Yongquan Lin, Zhilong Yang, Juan Tan, Wentao Qiao
Summary: This study investigated the mechanism of upregulation of c-fos mRNA translation efficiency when cellular protein synthesis is shut off. The results showed that EV71 infection led to increased levels of c-Fos protein expression in rhabdomyosarcoma cells. Further analysis revealed the role of PCBP2 and La in regulating the IRES activity of c-fos, providing a novel target for gene translation regulation.
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Madelaine Magali Audero, Natalia Prevarskaya, Alessandra Fiorio Pla
Summary: This review presents the impact of hypoxia and acidosis in the tumor microenvironment (TME) on cancer progression, and focuses on the role of Ca2+ channels in this process.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Tiphaine Delaunay, Carole Achard, Nicolas Boisgerault, Marion Grard, Tacien Petithomme, Camille Chatelain, Soizic Dutoit, Christophe Blanquart, Pierre-Joseph Royer, Stephane Minvielle, Lisa Quetel, Clement Meiller, Didier Jean, Delphine Fradin, Jaafar Bennouna, Antoine Magnan, Laurent Cellerin, Frederic Tangy, Marc Gregoire, Jean-Francois Fonteneau
JOURNAL OF THORACIC ONCOLOGY
(2020)
Article
Oncology
Lisa Quetel, Clement Meiller, Jean-Baptiste Assie, Yuna Blum, Sandrine Imbeaud, Francois Montagne, Robin Tranchant, Julien de Wolf, Stefano Caruso, Marie-Christine Copin, Veronique Hofman, Laure Gibault, Cecile Badoual, Ecaterina Pintilie, Paul Hofman, Isabelle Monnet, Arnaud Scherpereel, Francoise Le Pimpec-Barthes, Jessica Zucman-Rossi, Marie-Claude Jaurand, Didier Jean
MOLECULAR ONCOLOGY
(2020)
Review
Oncology
Christophe Blanquart, Marie-Claude Jaurand, Didier Jean
FRONTIERS IN ONCOLOGY
(2020)
Letter
Oncology
Didier Jean, Tiphaine Delaunay, Clement Meiller, Nicolas Boisgerault, Marion Grard, Stefano Caruso, Christophe Blanquart, Emanuela Felley-Bosco, Jaafar Bennouna, Frederic Tangy, Marc Gregoire, Jean-Francois Fonteneau
JOURNAL OF THORACIC ONCOLOGY
(2020)
Article
Oncology
Thibaut Blondy, Senan Mickael d'Almeida, Tina Briolay, Julie Tabiasco, Clement Meiller, Anne-Laure Chene, Laurent Cellerin, Sophie Deshayes, Yves Delneste, Jean-Francois Fonteneau, Nicolas Boisgerault, Jaafar Bennouna, Marc Gregoire, Didier Jean, Christophe Blanquart
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2020)
Article
Genetics & Heredity
Clement Meiller, Francois Montagne, Theo Z. Hirsch, Stefano Caruso, Julien de Wolf, Quentin Bayard, Jean-Baptiste Assie, Lea Meunier, Yuna Blum, Lisa Quetel, Laure Gibault, Ecaterina Pintilie, Cecile Badoual, Sarah Humez, Francoise Galateau-Salle, Marie-Christine Copin, Eric Letouze, Arnaud Scherpereel, Jessica Zucman-Rossi, Francoise Le Pimpec-Barthes, Marie-Claude Jaurand, Didier Jean
Summary: This study investigated intra-tumor heterogeneity in malignant pleural mesothelioma (MPM) using the largest series to date and multi-omics profiling of a substantial series of multi-site tumor samples. The results revealed patient-dependent spatial heterogeneity at genetic, transcriptomic, and epigenetic levels, as well as changes in the immune landscape of the tumor microenvironment, supporting the need for multi-sampling for precision medicine.
Article
Medicine, Research & Experimental
Antonia Marazioti, Anthi C. Krontira, Sabine J. Behrend, Georgia A. Giotopoulou, Giannoula Ntaliarda, Christophe Blanquart, Hasan Bayram, Marianthi Iliopoulou, Malamati Vreka, Lilith Trassl, Mario A. A. Pepe, Caroline M. Hackl, Laura Klotz, Stefanie A. Weiss, Ina Koch, Michael Lindner, Rudolph A. Hatz, Juergen Behr, Darcy E. Wagner, Helen Papadaki, Sophia G. Antimisiaris, Didier Jean, Sophie Deshayes, Marc Gregoire, Ozgecan Kayalar, Deniz Mortazavi, Sukru Dilege, Serhan Tanju, Suat Erus, Omer Yavuz, Pinar Bulutay, Pinar Firat, Ioannis Psallidas, Magda Spella, Ioanna Giopanou, Ioannis Lilis, Anne-Sophie Lamort, Georgios T. Stathopoulos
Summary: A portion of human MPM cases have mutations in KRAS, and mouse models suggest that KRAS mutations can lead to MPM, especially when combined with TP53 deletion. These findings indicate that KRAS alterations may play an important and underestimated role in certain MPM patients.
EMBO MOLECULAR MEDICINE
(2022)
Article
Oncology
Marvin Martens, Franziska Kreidl, Friederike Ehrhart, Didier Jean, Merlin Mei, Holly M. Mortensen, Alistair Nash, Penny Nymark, Chris T. Evelo, Ferdinando Cerciello
Summary: Malignant pleural mesothelioma (MPM) is a highly aggressive malignancy mainly triggered by exposure to asbestos and characterized by complex biology. The research community has generated a significant body of knowledge over the decades to improve understanding of the disease for prevention, diagnostics, and new treatments. Developing integrated tools for accessing and analyzing data can aid scientists in studying and comprehending MPM more effectively.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Ananya Hariharan, Weihong Qi, Hubert Rehrauer, Licun Wu, Manuel Ronner, Martin Wipplinger, Jelena Kresoja-Rakic, Suna Sun, Lucia Oton-Gonzalez, Marika Sculco, Veronique Serre-Beinier, Clement Meiller, Christophe Blanquart, Jean-Francois Fonteneau, Bart Vrugt, Jan Hendrik Ruschoff, Isabelle Opitz, Didier Jean, Marc de Perrot, Emanuela Felley-Bosco
Summary: This study found increased levels of ADAR-mediated RNA editing in mesothelioma tumors and primary cultures compared to mesothelial cells. Heterogeneity in editing was observed between tumor samples and primary cultures. ADAR2 expression levels were higher in BRCA1-associated protein 1 wild-type tumors and correlated with changes in RNA editing in transcripts and 3'UTR. ADAR2 was found to play a role in cell proliferation, cell cycle, sensitivity to antifolate treatment, and type-1 interferon signaling, leading to changes in the microenvironment in vivo.
MOLECULAR ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Emanuela Felley-Bosco, Weihong Qi, Didier Jean, Clement Meiller, Hubert Rehrauer
Summary: This study reveals the association between RNA editing and the epithelial-mesenchymal transition (EMT) phenotype in pleural mesothelioma (PM). Analysis of RNA editing expression changes in PM samples showed increased editing in introns and decreased editing in 3' UTR in samples with EMT phenotype.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Sabine Paternot, Eric Raspe, Clement Meiller, Maxime Tarabichi, Jean-Baptiste Assie, Frederick Libert, Myriam Remmelink, Xavier Bisteau, Patrick Pauwels, Yuna Blum, Nolwenn Le Stang, Severine Tabone-Eglinger, Francoise Galateau-Salle, Christophe Blanquart, Jan P. Van Meerbeeck, Thierry Berghmans, Didier Jean, Pierre P. Roger
Summary: This study evaluated the impact of CDK4/6 inhibition by palbociclib in malignant pleural mesothelioma (MPM) and found that MPM is uniquely sensitive to CDK4/6 inhibitors. Palbociclib can durably inhibit cell proliferation, even after drug washout, and induce a senescence-associated secretory phenotype. The study supports the evaluation of CDK4/6 inhibitors as monotherapy or combination therapy for MPM treatment.
MOLECULAR ONCOLOGY
(2022)
Article
Immunology
Esther Stern, Stefano Caruso, Clement Meiller, Inbal Mishalian, Theo Z. Hirsch, Quentin Bayard, Carmit T. Tadmor, Hanna Wald, Didier Jean, Ori Wald
Summary: In this study, the AB12 murine mesothelioma model was thoroughly characterized to improve its accuracy in predicting the response of human malignant pleural mesothelioma (hMPM) to immunotherapy. The study found that different stages of tumors have different responses to immunotherapy, with intermediate tumors showing the best response and advanced tumors showing a weakening response. Additionally, the addition of cisplatin to the standard-of-care immunotherapy improved mice survival and enhanced the anti-tumor response in advanced tumors.
FRONTIERS IN IMMUNOLOGY
(2023)
Meeting Abstract
Oncology
L. Mangiante, N. Alcala, A. Di Genova, A. Sexton-Oates, N. Le Stang, S. Boyault, C. Cuenin, F. Damiola, C. Voegele, M. Mesobank, D. Jean, S. Lantuejoul, A. Ghantous, H. Hernandez-Vargas, C. Caux, N. Girard, N. Lopez-Bigas, L. B. Alexandrov, F. Galateau Salle, M. Foll, L. Fernandez-Cuesta
JOURNAL OF THORACIC ONCOLOGY
(2022)
Meeting Abstract
Oncology
Clement Meiller, Francois Montagne, Theo Z. Hirsch, Stefano Caruso, Julien de Wolf, Quentin Bayard, Jean-Baptiste Assie, Lea Meunier, Yuna Blum, Lisa Quetel, Laure Gibault, Ecaterina Pintilie, Cecile Badoual, Marie-Christine Copin, Eric Letouze, Arnaud Scherpereel, Jessica Zucman-Rossi, Francoise Le Pimpec-Barthes, Marie-Claude Jaurand, Didier Jean
Meeting Abstract
Oncology
Anne Soude, Martine Barth, Jean-Michel Luccarini, Severine Delaporte, Florence Chirade, Christelle Valaire, Aude Boulay, Genevieve Cheret, Marie Dorchie, Celine Estivalet, Pascale Tuya-Boustugue, Robin Tranchand, Didier Jean, Lisa Quetel, Jean-Baptiste Assie, Irena Konstantinova, Jean-Louis Junien, Pierre Broqua
MOLECULAR CANCER RESEARCH
(2020)