Article
Biochemistry & Molecular Biology
Hiba A. Al-Ashtal, Courtney M. Rubottom, Thomas C. Leeper, Andrea J. Berman
Summary: LARP1 is an RNA-binding protein that regulates the stability and translation of mRNAs encoding the translation machinery by recognizing TOP motifs and poly(A) RNA simultaneously.
Article
Biochemistry & Molecular Biology
Jian-Jun Jia, Roni M. Lahr, Michael T. Solgaard, Bruno J. Moraes, Roberta Pointet, An-Dao Yang, Giovanna Celucci, Tyson E. Graber, Huy-Dung Hoang, Marius R. Niklaus, Izabella A. Pena, Anne K. Hollensen, Ewan M. Smith, Malik Chaker-Margot, Leonie Anton, Christopher Dajadian, Mark Livingstone, Jaclyn Hearnden, Xu-Dong Wang, Yonghao Yu, Timm Maier, Christian K. Damgaard, Andrea J. Berman, Tommy Alain, Bruno D. Fonseca
Summary: The study reveals that mTORC1 controls TOP mRNA translation repression activity through phosphorylating LARP1, with some residues being especially sensitive to rapamycin. This phosphorylation affects the RNA-binding and translation inhibitory activities of LARP1, providing insights into a new model of translation control involving differentially regulated regions of LARP1.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Zeenat Farooq, Fedho Kusuma, Phillip Burke, Catherine R. Dufour, Duckgue Lee, Negar Tabatabaei, Phoenix Toboz, Ernest Radovani, Jack F. Greenblatt, Jalees Rehman, Jacob Class, Arkady Khoutorsky, Bruno D. Fonseca, Justin M. Richner, Eloi Mercier, Guillaume Bourque, Vincent Giguere, Arvind R. Subramaniam, Jaeseok Han, Soroush Tahmasebi
Summary: In this study, the researchers identify the involvement of the nutrient sensing kinase GCN2 in regulating LARP1-mediated inhibition of TOP mRNA translation. They demonstrate that GCN2 controls LARP1 activity through two mechanisms: ATF4-dependent transcriptional induction of LARP1 mRNA and GCN1-mediated recruitment of LARP1 to stalled ribosomes. These findings provide new insights into the regulation of TOP mRNA translation and shed light on the role of GCN2 in this process.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Irmgard U. Haussmann, Yanying Wu, Mohanakarthik P. Nallasivan, Nathan Archer, Zsuzsanna Bodi, Daniel Hebenstreit, Scott Waddell, Rupert Fray, Matthias Soller
Summary: Two cap methyltransferases in Drosophila can methylate the ribose of the first nucleotide in mRNA, contributing to reward learning and localization of untranslated mRNAs to synapses.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Farnaz Mansouri-Noori, Andreas Pircher, Danielle Bilodeau, Lidia Siniavskaia, Jorg Grigull, Olivia S. Rissland, Mark A. Bayfield
Summary: This study reveals that the fission yeast LARP1 homolog, Slr1p, controls the translation and stability of mRNAs encoding proteins similar to 5'TOP mRNAs in higher eukaryotes. It suggests that the LARP1 DM15 motif and the mRNA 5'TOP motif may be features that were formed based on a more fundamental mechanism of LARP1-associated control of gene expression.
Article
Cell Biology
Koichi Ogami, Yuka Oishi, Kentaro Sakamoto, Mayu Okumura, Ryota Yamagishi, Takumi Inoue, Masaya Hibino, Takuto Nogimori, Natsumi Yamaguchi, Kazuya Furutachi, Nao Hosoda, Hiroto Inagaki, Shin-ichi Hoshino
Summary: Translation of 5' terminal oligopyrimidine (TOP) mRNAs encoding the protein synthesis machinery is regulated by an amino-acid-sensing mTOR pathway. The poly(A) tail length of TOP mRNAs dynamically fluctuates in response to amino acid availability. LARP1 interacts with non-canonical poly(A) polymerases and induces post-transcriptional polyadenylation of the target, contributing to the selective accumulation of long poly(A) tailed TOP mRNAs under amino-acid-starved conditions.
Review
Immunology
Andrei A. Deviatkin, Ruslan A. Simonov, Kseniya A. Trutneva, Anna A. Maznina, Anastasiia B. Soroka, Anna A. Kogan, Sofya G. Feoktistova, Elena M. Khavina, Olga N. Mityaeva, Pavel Y. Volchkov
Summary: Recently, the mRNA platform has become the method of choice in vaccine development to find new ways to fight infectious diseases. However, mRNA vaccines have the drawback of requiring special storage conditions, making them less accessible. Circular mRNAs have been proposed as a solution to this problem, as they lack the ends that are susceptible to degradation. This review summarizes the current knowledge on cap-independent translation initiation methods for circular mRNAs and discusses their potential effectiveness in developing vaccines and other biotechnological products.
Article
Biochemistry & Molecular Biology
Alison Galloway, Aneesa Kaskar, Dimitrinka Ditsova, Abdelmadjid Atrih, Harunori Yoshikawa, Carolina Gomez-Moreira, Olga Suska, Marcin Warminski, Renata Grzela, Angus Lamond, Edward Darzynkiewicz, Jacek Jemielity, Victoria H. Cowling
Summary: The study reveals that RNMT plays a crucial role in T cell activation by regulating ribosome biogenesis, which is essential for cellular metabolic reprogramming, proliferation, and differentiation. RNMT selectively regulates the expression of mRNAs targeted by the (m7)G-cap binding protein LARP1, impacting ribosome synthesis and translation rates.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Gastroenterology & Hepatology
Komal Ramani, Aaron E. Robinson, Joshua Berlind, Wei Fan, Aushinie Abeynayake, Aleksandra Binek, Lucia Barbier-Torres, Mazen Noureddin, Nicholas N. Nissen, Zehra Yildirim, Ebru Erbay, Jose M. Mato, Jennifer E. Van Eyk, Shelly C. Lu
Summary: Our study identified a SAMe-sensitive mechanism of LARP1 phosphorylation that may be involved in the progression from NASH to HCC.
Article
Cell & Tissue Engineering
Marino Caruso, Damien Detraux, Amandine Mathieu, Manon Gilson, Marc Dieu, Antoine Fattaccioli, Catherine Demazy, Mustapha Najimi, Etienne Sokal, Thierry Arnould, Catherine Verfaillie, Denis L. J. Lafontaine, Patricia Renard
Summary: Translational regulation plays a crucial role in proteome remodeling during stem cell differentiation. This study investigated translational remodeling during hepatogenic differentiation of induced pluripotent stem cells (iPSCs) using polysome profiling. The findings suggest that protein synthesis increases during the initial stages of hepatogenic differentiation and is then globally repressed during later stages. However, despite the overall translational repression, key hepatogenic genes are efficiently translated and even induced for transcripts involved in hepatospecific functions and metabolic maturation.
Article
Biochemistry & Molecular Biology
Martyna Nowacka, Przemyslaw Latoch, Matylda A. Izert, Natalia K. Karolak, Rafal Tomecki, Michal Koper, Agnieszka Tudek, Agata L. Starosta, Maria W. Gorna
Summary: This study proposes an mRNA enrichment strategy based on the RNA-binding properties of human IFIT1, which effectively depletes rRNA while maintaining high quality RNA-seq data with coverage of the protein coding transcriptome. It is a cost-effective and versatile tool for preparing mRNA libraries for various organisms.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Guennadi Kozlov, Sandy Mattijssen, Jianning Jiang, Samuel Nyandwi, Tara Sprules, James R. Iben, Steven L. Coon, Sergei Gaidamakov, Anne M. Noronha, Christopher J. Wilds, Richard J. Maraia, Kalle Gehring
Summary: In this study, the La-module of LARP1 was characterized, and it was found that unlike other LARPs, the La-module of LARP1 does not contain an RRM domain. The La-module alone is capable of binding poly(A) RNA with high specificity for the RNA 3'-end. This study provides insights into the functional relevance of LARP1 RNA binding in cells.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Cell Biology
Cornelius Schneider, Florian Erhard, Beyenech Binotti, Alexander Buchberger, Jorg Vogel, Utz Fischer
Summary: In starvation conditions, 5'TOP mRNAs undergo low baseline translation with reduced initiation rates instead of being translationally silenced, ensuring a stable 5'TOP mRNA population and allowing fast reversibility of translational repression.
Article
Multidisciplinary Sciences
Fatima Cairrao, Cristiana C. Santos, Adrien Le Thomas, Scot Marsters, Avi Ashkenazi, Pedro M. Domingos
Summary: This study reveals that the mRNA binding protein Pumilio in fruit flies can protect Xbp1 mRNA from the non-canonical endoribonuclease activity of Ire1 by binding to it. The phosphorylation of Pumilio is crucial for its stabilization of Xbp1 mRNA.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Dennis Reichert, Henning D. Mootz, Andrea Rentmeister
Summary: Gene expression is tightly regulated with post-transcriptional regulation more pronounced in higher eukaryotes. Optochemical and optogenetic approaches enable the actuation of underlying processes by light. Research has shown that light can induce increased translation activity in eukaryotes.
Article
Chemistry, Organic
Mary Anne Maverick, Marie Gaillard, Jean-Jacques Vasseur, Francoise Debart, Michael Smietana
Summary: Research on the chemical functionalization at the C-5' position of nucleosides has been relatively limited, despite its potential significant role for biological activity. A new Pd-catalyzed and Cu(I)-mediated reaction method was developed in this study to synthesize diversely modified 5'-acyl nucleosides, paving the way for the preparation of a variety of potentially bioactive compounds.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Review
Chemistry, Organic
Rostom Ahmed-Belkacem, Francoise Debart, Jean-Jacques Vasseur
Summary: Bisubstrate strategies address the lack of specificity in targeting methyltransferases by mimicking the transition state complex. These inhibitors have the potential to be selective therapeutics for cancers, neuropsychiatric disorders, and viral infections.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Rostom Ahmed-Belkacem, Marcel Hausdorff, Adrien Delpal, Priscila Sutto-Ortiz, Agathe M. G. Colmant, Franck Touret, Natacha S. Ogando, Eric J. Snijder, Bruno Canard, Bruno Coutard, Jean-Jacques Vasseur, Etienne Decroly, Francoise Debart
Summary: This study focuses on the design and synthesis of inhibitors against SARS-CoV-2 enzymes involved in RNA capping, which are important for viral RNA stability, mRNA translation, and evasion of innate immunity. Seven compounds showed significant inhibitory activity, and the three most potent inhibitors stabilized the enzyme effectively.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Lorene Gonnin, Charles-Adrien Richard, Irina Gutsche, Didier Chevret, Joris Troussier, Jean-Jacques Vasseur, Francoise Debart, Jean-Francois Eleoue, Marie Galloux
Summary: Respiratory syncytial virus has a negative-sense single-stranded RNA genome encapsidated by the viral nucleoprotein N. The recruitment of L protein onto the nucleoprotein depends on the viral phosphoprotein P. The interaction between P and N complexed with RNA is responsible for the morphogenesis of viral factories.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
A. Mills, N. Aissaoui, D. Maurel, J. Elezgaray, F. Morvan, J. J. Vasseur, E. Margeat, R. B. Quast, J. Lai Kee-Him, N. Saint, C. Benistant, A. Nord, F. Pedaci, G. Bellot
Summary: This study introduces a programmable DNA origami-based molecular actuator called Nano-winch, which can manipulate multiple mechanoreceptors by exerting fine-tuned forces. This device provides a tool-free approach to control and explore mechanotransduction circuits on living cells.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Ashleigh Shannon, Bhawna Sama, Pierre Gauffre, Theo Guez, Francoise Debart, Jean-Jacques Vasseur, Etienne Decroly, Bruno Canard, Francois Ferron
Summary: In this study, we discovered that the ORF1a region of certain members of the large genome Tobaniviridae family indeed harbors N7-specific methyltransferase activity. We presented its structure as the first N7-specific Rossmann-fold (RF) methyltransferase identified for (+)RNA viruses, which is remarkably different from that of the known Coronaviridae ORF1b N7-MTase gene. The appearance of this methyltransferase in an unexpected location in the genome introduces a split-off in the classification of Tobaniviridae.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Kevan Perez de Carvasal, Gerard Vergoten, Jean-Jacques Vasseur, Michael Smietana, Francois Morvan
Summary: Inspired by automated DNA synthesis, phosphodiester-linked homohexamers consisting of an electron-rich DAN donor and an electron-deficient NDI acceptor were synthesized, resulting in flexible and hydrophilic hexamers. These hexamers formed fibers and hydrogels through charge transfer donor-acceptor recognition, with the resulting structure-dependent on the nature of the complementary partner.
Article
Biochemistry & Molecular Biology
Priscila El Kazzi, Nadia Rabah, Celia Chamontin, Lina Poulain, Francois Ferron, Francoise Debart, Bruno Canard, Dorothee Misse, Bruno Coutard, Sebastien Nisole, Etienne Decroly
Summary: This study reveals that the 2' O-methylation marks inside the HIV-1 genome help the virus evade the host immune system. The virus achieves self-methylation by recruiting the cellular methyltransferase FTSJ3, which allows it to avoid detection by the antiviral protein ISG20. This mechanism enables HIV-1 to replicate and spread more effectively.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Mikael Feracci, Cecilia Eydoux, Veronique Fattorini, Lea Lo Bello, Pierre Gauffre, Barbara Selisko, Priscila Sutto-Ortiz, Ashleigh Shannon, Hongjie Xia, Pei-Yong Shi, Mathieu Noel, Francoise Debart, Jean-Jacques Vasseur, Steve Good, Kai Lin, Adel Moussa, Jean-Pierre Sommadossi, Aurelie Chazot, Karine Alvarez, Jean-Claude Guilemot, Etinne Decroly, Francois Ferron, Bruno Canard
Summary: AT-752 is a guanosine analogue prodrug that is active against dengue virus (DENV) by inhibiting RNA synthesis. It targets the RNA 2'-O-MTase and RNA-dependent RNA polymerase (RdRp) activities of NS5. The crystal structure and activities of the DENV 2 MTase domain in complex with AT-9010 show its binding to the GTP/RNA-cap binding site, resulting in the inhibition of 2'-O but not N7-methylation activity.
ANTIVIRAL RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Mathieu Noel, Theo Guez, Yann Thillier, Jean-Jacques Vasseur, Francoise Debart
Summary: The importance of mRNA with 5'-cap emphasizes the need for efficient access to RNA substrates with different (7m)G caps. This research presents a novel all-chemical method for synthetic RNA capping, which involves solid-phase chemistry and automated RNA assembly. The method allows for the production of high-purity (7m)G-cap RNA with various cap structures, providing valuable research tools to study cap-related processes.
Article
Chemistry, Medicinal
Marcel Hausdorff, Adrien Delpal, Sarah Barelier, Laura Nicollet, Bruno Canard, Franck Touret, Agathe Colmant, Bruno Coutard, Jean-Jacques Vasseur, Etienne Decroly, Francoise Debart
Summary: The COVID-19 pandemic has raised the urgent need for new therapeutic drugs targeting the SARS-CoV-2 replication machinery. This study focuses on the development of inhibitors targeting the highly conserved protein nsp14, which is involved in viral RNA translation and immune evasion. Through structure-guided drug design, 26 novel adenosine mimetics were synthesized, one of which showed selective inhibition of nsp14 N7-MTase activity with high potency against SARS-CoV-2 replication in cell culture.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Organic
Mary Anne Maverick, Mathieu Noel, Jean-Jacques Vasseur, Carine Baraguey, Francoise Debart, Michael Smietana
Summary: It has been observed that 2',3'-O-isopropylidene analogue of N4-acetylcytidine undergoes an unprecedented oxidative cyclization in the presence of hypervalent iodine(III) in water, resulting in a mixture of C5-substituted O6,5'-cyclo-5,6-dihydrouridines. These cyclouridines can be opened under basic conditions and further synthesized into an important post-transcriptional modification of bacterial tRNA.
Article
Chemistry, Organic
Romain Amador, Adrien Delpal, Bruno Canard, Jean-Jacques Vasseur, Etienne Decroly, Francoise Debart, Guillaume Clave, Michael Smietana
Summary: N-Acylsulfonamides, possessing unique physico-chemical properties, have attracted increasing interest in medicinal chemistry. This study demonstrates the easy and efficient synthesis of N-acylsulfonamide analogues via the sulfo-click reaction.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
