Article
Cell Biology
Un Yung Choi, Jae Jin Lee, Angela Park, Kyle L. Jung, Shin-Ae Lee, Youn Jung Choi, Hye-Ra Lee, Chih-Jen Lai, Hyungjin Eoh, Jae U. Jung
Summary: KSHV hijacks spermidine synthesis and eIF5A hypusination pathways to enhance LANA expression for viral episomal maintenance, suggesting polyamine metabolism and eIF5A hypusination as therapeutic targets for KSHV-induced tumorigenesis.
Article
Multidisciplinary Sciences
Victor Faundes, Martin D. Jennings, Siobhan Crilly, Sarah Legraie, Sarah E. Withers, Sara Cuvertino, Sally J. Davies, Andrew G. L. Douglas, Andrew E. Fry, Victoria Harrison, Jeanne Amiel, Daphne Lehalle, William G. Newman, Patricia Newkirk, Judith Ranells, Miranda Splitt, Laura A. Cross, Carol J. Saunders, Bonnie R. Sullivan, Jorge L. Granadillo, Christopher T. Gordon, Paul R. Kasher, Graham D. Pavitt, Siddharth Banka
Summary: The study uncovers the role of eIF5A in human development and disease, demonstrates the mechanistic complexity of EIF5A-related disorder, and raises possibilities for its treatment. Yeast and zebrafish experiments show that EIF5A variants cause a Mendelian disorder through reduced eIF5A-ribosome interactions, which can be partially corrected by spermidine supplementation.
NATURE COMMUNICATIONS
(2021)
Article
Microbiology
Mason R. Firpo, Natalie J. LoMascolo, Marine J. Petit, Priya S. Shah, Bryan C. Mounce
Summary: Viruses rely on cellular metabolism for infection, and it has been discovered that polyamines regulate cholesterol synthesis, which affects viral attachment. The role of polyamines in translation is crucial for their regulation of cholesterol synthesis.
Review
Biochemistry & Molecular Biology
Aristeidis Panagiotis Sfakianos, Rebecca Mallory Raven, Anne Elizabeth Willis
Summary: Protein synthesis dysregulation in cancer provides a promising therapeutic target. The elongation factor eIF5A, involved in protein elongation and with multiple functions in cellular processes, is being considered as a potential target for cancer treatment. Inhibitors of eIF5A are under development as anti-cancer agents.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2022)
Article
Cell Biology
Xiaoxiao Ouyang, Xueyun Wang, Pan Li, Qin Huang, Li Zhou, Jingxiang Li, Li Gao, Qi Sun, Fangni Chai, Shupan Guo, Zhihui Zhou, Xin Liu, Lunzhi Dai, Wei Cheng, Haiyan Ren
Summary: In this study, the host protein ZPR1 was identified as an interacting partner of the EPEC effector NleE through protein crosslinking. It was found that ZPR1 regulates CHOP-mediated UPRER at the transcriptional level through liquid-liquid phase separation. Interestingly, NleE disrupts the binding ability of ZPR1 with K63-ubiquitin chains, which promotes its liquid-liquid phase separation. Further analysis showed that EPEC restricts host UPRER pathways at the transcription level in a cascade-dependent manner between NleE and ZPR1. Overall, this study reveals the mechanism by which EPEC interferes with CHOP-UPRER through regulating ZPR1 to facilitate immune evasion.
Article
Biochemistry & Molecular Biology
Sebastian Filbeck, Federico Cerullo, Helge Paternoga, George Tsaprailis, Claudio A. P. Joazeiro, Stefan Pfeffer
Summary: The study found that aborted translation leads to large ribosomal subunits obstructed with tRNA-linked nascent chains, which are substrates of ribosome-associated quality control. Bacterial RqcH, a widely conserved RQC factor, can modify the C-termini of nascent chains to form a polyalanine degron. The research revealed the mechanism of tRNA selection and the role of RqcH in the synthesis of nascent chains.
Article
Hematology
Pedro Gonzalez-Menendez, Ira Phadke, Meagan E. Olive, Axel Joly, Julien Papoin, Hongxia Yan, Jeremy Galtier, Jessica Platon, Sun Woo Sophie Kang, Kathy L. McGraw, Marie Daumur, Marie Pouzolles, Taisuke Kondo, Stephanie Boireau, Franciane Paul, David J. Young, Sylvain Lamure, Raghavendra G. Mirmira, Anupama Narla, Guillaume Cartron, Cynthia E. Dunbar, Myriam Boyer-Clavel, Natalie Porat-Shliom, Valerie Dardalhon, Valderie S. Zimmermann, Marc Sitbon, Thomas E. Dever, Narla Mohandas, Lydie Da Costa, Namrata D. Udeshi, Lionel Blanc, Sandrina Kinet, Naomi Taylor
Summary: This study demonstrates that metabolic programs play a role in the fate of hematopoietic stem and progenitor cells (HSPCs), and the metabolic regulation of protein synthesis controls HSPC differentiation. The researchers found that the uptake of arginine and its catabolism to spermidine control erythroid specification of HSPCs through the activation of eIF5A. The study also reveals the importance of mitochondrial translation and oxidative phosphorylation in eIF5A-regulated erythropoiesis. Rating: 8/10
Article
Biochemistry & Molecular Biology
Aleksandra E. Korenskaia, Yury G. Matushkin, Sergey A. Lashin, Alexandra Klimenko
Summary: This study evaluates the correlation between experimentally measured protein abundance and predicted translation elongation efficiency characteristics for 26 prokaryotes. Results show that, for some organisms, secondary structures are better predictors of protein abundance than codon usage bias. Several factors, including elongation efficiency optimization type, taxonomical identity, and growth rate, are associated with the value of the correlation coefficient.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Microbiology
Guillaume N. Fiches, Zhenyu Wu, Dawei Zhou, Ayan Biswas, Tai-Wei Li, Weili Kong, Maxime Jean, Netty G. Santoso, Jian Zhu
Summary: Understanding the dynamic interaction between KSHV and host metabolic pathways is important for developing therapies for KSHV-associated malignancies. In this study, we showed that KSHV modulates polyamine metabolism to promote eIF5A hypusination and translation of critical KSHV proteins. We also demonstrated that inhibitors targeting these pathways can effectively suppress KSHV infection. These findings provide new insights into KSHV-induced alterations of host metabolism and offer potential therapeutic targets for treating KSHV-associated malignancies.
Review
Biochemistry & Molecular Biology
Marina Barba-Aliaga, Paula Alepuz
Summary: The eukaryotic translation initiation factor 5A (eIF5A) plays a crucial role in translation and cellular processes. It has been associated with various diseases and proposed as an anti-aging factor. Recent research has revealed its important function in maintaining healthy mitochondria, although the precise mechanisms are still unclear. This review discusses the link between eIF5A and mitochondria, speculates on its role in regulating mitochondrial homeostasis, and highlights its potential as a target in diseases related to energy metabolism.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Lauren Forbes Beadle, Jennifer L. Love, Yuliya Shapovalova, Artem Artemev, Magnus Rattray, Hilary Ashe
Summary: This article explores the importance of mRNA degradation regulation and the establishment of mature mRNA dynamics in the early Drosophila embryo. The study reveals a correlation between short-lived mRNA and association with P-bodies, as well as enrichment of mRNA 3' ends in P-bodies during early embryogenesis.
Article
Biochemistry & Molecular Biology
Takahiro Suzuki, Kosuke Ito, Tomohiro Miyoshi, Ryo Murakami, Toshio Uchiumi
Summary: The ribosomal stalk protein aP1 binds to aEF1A in two different modes, with aEF1B playing a role in nucleotide exchange and enhancing polyphenylalanine synthesis. The crystal structure of the aEF1A.aEF1B complex shows a conformational change that disrupts the original aP1 binding site, suggesting aEF1B's role in promoting translation elongation.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Cell Biology
Marina Barba-Aliaga, Adriana Mena, Vanessa Espinoza, Nadezda Apostolova, Mercedes Costell, Paula Alepuz
Summary: The translation of mRNAs encoding consecutive proline sequences requires the elongation factor eIF5A, and its depletion leads to stalled translation and ER stress in collagen synthesis. Depletion of eIF5A interrupts translation at Pro-Gly collagenic motifs and reduces collagen production, suggesting eIF5A as a potential target for regulating fibrotic diseases.
JOURNAL OF CELL SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Alexander Zhdanov, Anna Golubeva, Martina M. Yordanova, Dmitry E. Andreev, Ana Paula Ventura-Silva, Harriet Schellekens, Pavel Baranov, John F. Cryan, Dmitri B. Papkovsky
Summary: Activated ghrelin receptor GHS-R1 alpha regulates energy homeostasis and biosynthetic processes. New research shows that ghrelin can rapidly enhance protein synthesis in cells by dephosphorylating eEF2. This translation activation process may contribute to the rapid replenishment of neuropeptides released upon GHS-R1a activation.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Joanna R. Kovalski, Duygu Kuzuoglu-Ozturk, Davide Ruggero
Summary: This review discusses how cancer cells regulate protein expression through translational control and highlights the clinical potential of targeting translation factors as anti-cancer therapies. It also details the interaction between RNA sequence and structural elements, the translational machinery, and RNA-binding proteins in coordinating specific pro-survival and pro-growth programs. Additionally, the review provides an overview of current and emerging technologies for studying selective translational control in cancer cells and the tumor microenvironment.
Article
Multidisciplinary Sciences
Nicholas E. Phillips, Aleksandra Mandic, Saeed Omidi, Felix Naef, David M. Suter
NATURE COMMUNICATIONS
(2019)
Article
Multidisciplinary Sciences
Charlotte N. Hor, Jake Yeung, Maxime Jan, Yann Emmenegger, Jeffrey Hubbard, Ioannis Xenarios, Felix Naef, Paul Franken
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2019)
Article
Multidisciplinary Sciences
Cedric Gobet, Benjamin Dieter Weger, Julien Marquis, Eva Martin, Nagammal Neelagandan, Frederic Gachon, Felix Naef
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Multidisciplinary Sciences
Benjamin D. Weger, Cedric Gobet, Fabrice P. A. David, Florian Atger, Eva Martin, Nicholas E. Phillips, Aline Charpagne, Meltem Weger, Felix Naef, Frederic Gachon
Summary: The study investigated the roles of the circadian clock and feeding rhythms in regulating rhythmic gene expression in the liver, highlighting their importance and differential contributions. Both feeding patterns and the circadian clock influence gene expression rhythms, with distinct amplitudes. By analyzing multiple core clock regulators, the research revealed their varying impacts on liver gene expression regulation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Genetics & Heredity
Jerome Mermet, Jake Yeung, Felix Naef
Summary: The study reveals that both clock-controlled and clock-independent chromatin topology play a role in regulating the rhythmic physiology of the liver in mice. Dynamic and static DNA contacts contribute to the circadian transcription of liver physiology.
Article
Biochemistry & Molecular Biology
Nicholas E. Phillips, Alice Hugues, Jake Yeung, Eric Durandau, Damien Nicolas, Felix Naef
Summary: Research on single-cell mRNA dynamics of core clock genes in mouse fibroblasts using single-molecule fluorescence technology revealed significant variability between cells. A probabilistic model was developed to account for transcriptional bursting, circadian time, and cell-to-cell heterogeneity, with clock time contributing only a small fraction to mRNA number variability between cells.
MOLECULAR SYSTEMS BIOLOGY
(2021)
Editorial Material
Multidisciplinary Sciences
Katharine C. Abruzzi, Cedric Gobet, Felix Naef, Michael Rosbash
Summary: The study by Ray et al. claimed the presence of temperature-compensated free-running mRNA oscillations in Bmal1(-/-) liver slices and skin fibroblasts. However, upon reanalysis, fewer reproducible mRNA oscillations were found in this genotype, along with errors and potentially inappropriate analyses.
Article
Biology
Kawssar Harb, Melanie Richter, Nagammal Neelagandan, Elia Magrinelli, Hend Harfoush, Katrin Kuechler, Melad Henis, Irm Hermanns-Borgmeyer, Froylan Calderon de Anda, Kent Duncan
Summary: RNA-binding proteins play a role in defining area-specific cytoarchitecture in the neocortex. They interact with and affect the translation of mRNAs encoding specific proteins involved in neuronal specification. The post-transcriptional regulation mediated by these proteins contributes to the development of area-specific neuronal identity and connectivity in the neocortex.
Article
Genetics & Heredity
Clemence S. Hurni, Benjamin Weger, Cedric S. Gobet, Felix Naef
Summary: This study analyzed the temporal regulation of RNA synthesis, splicing, nuclear export, and degradation in eukaryotes, specifically focusing on the circadian cycle. The researchers found that nuclear export contributes to the modulation and generation of rhythmic profiles of 10% of the cycling nuclear mRNAs.
Article
Multidisciplinary Sciences
Lorenzo Talamanca, Cedric Gobet, Felix Naef
Summary: The study revealed that the circadian clock regulates human physiology, but the specific gene expression rhythms and their dependence on age and sex in humans were not well-defined. By combining data from the GTEx project and an algorithm, the researchers identified mRNA rhythms in 46 tissues and found that they varied in breadth and were affected by sex and age. The overall gene expression rhythms were more sustained in females, while rhythmic programs generally dampened with age.
Article
Endocrinology & Metabolism
Colas Droin, Jakob El Kholtei, Keren Bahar Halpern, Clemence Hurni, Milena Rozenberg, Sapir Muvkadi, Shalev Itzkovitz, Felix Naef
Summary: This study reveals the interplay between gene regulation in space and time in the liver using single-cell RNA-seq, showing that many genes exhibit both zonation and rhythmic expression, covering key hepatic functions as well as other processes such as protein chaperones. Additionally, the expression of Wnt target genes is shown to be rhythmic and localized, potentially influenced by rhythmically expressed Wnt ligands from non-parenchymal cells near the central vein.
