Olivier Namy

Scopus Publications

Correction to: Unveiling conserved HIV-1 open reading frames encoding T cell antigens using ribosome profiling (Nature Communications, (2025), 16, 1, (1707), 10.1038/s41467-025-56773-2)
Lisa Bertrand, Annika Nelde, Bertha Cecilia Ramirez, Isabelle Hatin, Hugo Arbes, Pauline François, Stéphane Demais, Emmanuel Labaronne, Didier Decimo, Laura Guiguettaz,et al.
Springer Science and Business Media LLC

Non-AUG HIV-1 uORF translation elicits specific T cell immune response and regulates viral transcript expression
Emmanuel Labaronne, Didier Décimo, Lisa Bertrand, Laura Guiguettaz, Thibault J. M. Sohier, David Cluet, Valérie Vivet-Boudou, Ana Luiza Chaves Valadão, Clara Dahoui, Pauline François,et al.
Springer Science and Business Media LLC

Unveiling conserved HIV-1 open reading frames encoding T cell antigens using ribosome profiling
Lisa Bertrand, Annika Nelde, Bertha Cecilia Ramirez, Isabelle Hatin, Hugo Arbes, Pauline François, Stéphane Demais, Emmanuel Labaronne, Didier Decimo, Laura Guiguettaz,et al.
Springer Science and Business Media LLC

Guidelines for minimal reporting requirements, design and interpretation of experiments involving the use of eukaryotic dual gene expression reporters (MINDR)
Gary Loughran, Dmitry E. Andreev, Ilya M. Terenin, Olivier Namy, Martin Mikl, Martina M. Yordanova, C. Joel McManus, Andrew E. Firth, John F. Atkins, Christopher S. Fraser,et al.
Springer Science and Business Media LLC

Aminoglycoside tolerance in Vibrio cholerae engages translational reprogramming associated with queuosine tRNA modification
Louna Fruchard, Anamaria Babosan, Andre Carvalho, Manon Lang, Blaise Li, Magalie Duchateau, Quentin Giai Gianetto, Mariette Matondo, Frederic Bonhomme, Isabelle Hatin,et al.
eLife Sciences Publications, Ltd
Tgt is the enzyme modifying the guanine (G) in tRNAs with GUN anticodon to queuosine (Q). tgt is required for optimal growth of Vibrio cholerae in the presence of sub-lethal aminoglycoside concentrations. We further explored here the role of the Q34 in the efficiency of codon decoding upon tobramycin exposure. We characterized its impact on the overall bacterial proteome, and elucidated the molecular mechanisms underlying the effects of Q34 modification in antibiotic translational stress response. Using molecular reporters, we showed that Q34 impacts the efficiency of decoding at tyrosine TAT and TAC codons. Proteomics analyses revealed that the anti-SoxR factor RsxA is better translated in the absence of tgt. RsxA displays a codon bias toward tyrosine TAT and overabundance of RsxA leads to decreased expression of genes belonging to SoxR oxidative stress regulon. We also identified conditions that regulate tgt expression. We propose that regulation of Q34 modification in response to environmental cues leads to translational reprogramming of transcripts bearing a biased tyrosine codon usage. In silico analysis further identified candidate genes which could be subject to such translational regulation, among which DNA repair factors. Such transcripts, fitting the definition of modification tunable transcripts, are central in the bacterial response to antibiotics.

Intricate ribosome composition and translational reprogramming in epithelial-mesenchymal transition
Chloé Morin, Agnès Baudin-Baillieu, Flora Nguyen Van Long, Caroline Isaac, Laure Bidou, Hugo Arbes, Pauline François, Roxane M. Pommier, Annie Adrait, Akari Saku,et al.
Proceedings of the National Academy of Sciences
Epithelial–mesenchymal transition (EMT) involves profound changes in cell morphology, driven by transcriptional and epigenetic reprogramming. However, evidence suggests that translation and ribosome composition also play key roles in establishing pathophysiological phenotypes. Using genome-wide analyses, we reported significant rearrangement of the translational landscape and machinery during EMT. Specifically, a cell line overexpressing the EMT transcription factor ZEB1 displayed alterations in translational reprogramming and fidelity. Furthermore, using riboproteomics, we unveiled an increased level of the ribosomal protein RPL36A in mesenchymal ribosomes, indicating precise tuning of ribosome composition. Remarkably, RPL36A overexpression alone was sufficient to trigger the acquisition of mesenchymal features, including a switch in the molecular pattern, cell morphology, and behavior, demonstrating its pivotal role in EMT. These findings underline the importance of translational reprogramming and fine-tuning of ribosome composition in EMT.

The ribosome profiling landscape of yeast reveals a high diversity in pervasive translation
Chris Papadopoulos, Hugo Arbes, David Cornu, Nicolas Chevrollier, Sandra Blanchet, Paul Roginski, Camille Rabier, Safiya Atia, Olivier Lespinet, Olivier Namy,et al.
Springer Science and Business Media LLC

TLN468 changes the pattern of tRNA used to read through premature termination codons in CFTR
Sabrina Karri, David Cornu, Claudia Serot, Lynda Biri, Aurélie Hatton, Elise Dréanot, Camille Rullaud, Iwona Pranke, Isabelle Sermet-Gaudelus, Alexandre Hinzpeter,et al.
Elsevier BV

Pervasive translation of Xrn1-sensitive unstable long noncoding RNAs in yeast
Sara ANDJUS, Ugo SZACHNOWSKI, Nicolas VOGT, Stamatia GIOFTSIDI, Isabelle HATIN, David CORNU, Chris PAPADOPOULOS, Anne LOPES, Olivier NAMY, Maxime WERY,et al.
Cold Spring Harbor Laboratory
Despite being predicted to lack coding potential, cytoplasmic long non-coding (lnc)RNAs can associate with ribosomes. However, the landscape and biological relevance of lncRNAs translation remains poorly studied. In yeast, cytoplasmic Xrn1-sensitive lncRNAs (XUTs) are targeted by the Nonsense-Mediated mRNA Decay (NMD), suggesting a translation-dependent degradation process. Here, we report that XUTs are pervasively translated, which impacts their decay. We show that XUTs globally accumulate upon translation elongation inhibition, but not when initial ribosome loading is impaired. Ribo-Seq confirmed ribosomes binding to XUTs and identified actively translated 5’-proximal small ORFs. Mechanistically, the NMD-sensitivity of XUTs mainly depends on the 3’-untranslated region length. Finally, we show that the peptide resulting from the translation of an NMD-sensitive XUT reporter exists in NMD-competent cells. Our work highlights the role of translation in the post-transcriptional metabolism of XUTs. We propose that XUT-derived peptides could be exposed to the natural selection, while NMD restricts XUTs levels.

The U UGA C sequence provides a favorable context to ELX-02 induced CFTR readthrough
Iwona M. Pranke, Jessica Varilh, Aurélie Hatton, Caroline Faucon, Emmanuelle Girodon, Elise Dreano, Benoit Chevalier, Sabrina Karri, Philippe Reix, Isabelle Durieu,et al.
Elsevier BV

2-Guanidino-quinazoline promotes the readthrough of nonsense mutations underlying human genetic diseases
Laure Bidou, Olivier Bugaud, Goulven Merer, Matthieu Coupet, Isabelle Hatin, Egor Chirkin, Sabrina Karri, Stéphane Demais, Pauline François, Jean-Christophe Cintrat,et al.
Proceedings of the National Academy of Sciences
Premature termination codons (PTCs) account for 10 to 20% of genetic diseases in humans. The gene inactivation resulting from PTCs can be counteracted by the use of drugs stimulating PTC readthrough, thereby restoring production of the full-length protein. However, a greater chemical variety of readthrough inducers is required to broaden the medical applications of this therapeutic strategy. In this study, we developed a reporter cell line and performed high-throughput screening (HTS) to identify potential readthrough inducers. After three successive assays, we isolated 2-guanidino-quinazoline (TLN468). We assessed the clinical potential of this drug as a potent readthrough inducer on the 40 PTCs most frequently responsible for Duchenne muscular dystrophy (DMD). We found that TLN468 was more efficient than gentamicin, and acted on a broader range of sequences, without inducing the readthrough of normal stop codons (TC).

Intergenic ORFs as elementary structural modules of de novo gene birth and protein evolution
Chris Papadopoulos, Isabelle Callebaut, Jean-Christophe Gelly, Isabelle Hatin, Olivier Namy, Maxime Renard, Olivier Lespinet, and Anne Lopes
Cold Spring Harbor Laboratory
The noncoding genome plays an important role in de novo gene birth and in the emergence of genetic novelty. Nevertheless, how noncoding sequences’ properties could promote the birth of novel genes and shape the evolution and the structural diversity of proteins remains unclear. Therefore, by combining different bioinformatic approaches, we characterized the fold potential diversity of the amino acid sequences encoded by all intergenic open reading frames (ORFs) of S. cerevisiae with the aim of (1) exploring whether the structural states’ diversity of proteomes is already present in noncoding sequences, and (2) estimating the potential of the noncoding genome to produce novel protein bricks that could either give rise to novel genes or be integrated into pre-existing proteins, thus participating in protein structure diversity and evolution. We showed that amino acid sequences encoded by most yeast intergenic ORFs contain the elementary building blocks of protein structures. Moreover, they encompass the large structural state diversity of canonical proteins, with the majority predicted as foldable. Then, we investigated the early stages of de novo gene birth by reconstructing the ancestral sequences of 70 yeast de novo genes and characterized the sequence and structural properties of intergenic ORFs with a strong translation signal. This enabled us to highlight sequence and structural factors determining de novo gene emergence. Finally, we showed a strong correlation between the fold potential of de novo proteins and one of their ancestral amino acid sequences, reflecting the relationship between the noncoding genome and the protein structure universe.

The importance of the Epi-transcriptome in translation fidelity
Charlène Valadon and Olivier Namy
MDPI AG
RNA modifications play an essential role in determining RNA fate. Recent studies have revealed the effects of such modifications on all steps of RNA metabolism. These modifications range from the addition of simple groups, such as methyl groups, to the addition of highly complex structures, such as sugars. Their consequences for translation fidelity are not always well documented. Unlike the well-known m6A modification, they are thought to have direct effects on either the folding of the molecule or the ability of tRNAs to bind their codons. Here we describe how modifications found in tRNAs anticodon-loop, rRNA, and mRNA can affect translation fidelity, and how approaches based on direct manipulations of the level of RNA modification could potentially be used to modulate translation for the treatment of human genetic diseases.

A Case of Gene Fragmentation in Plant Mitochondria Fixed by the Selection of a Compensatory Restorer of Fertility-Like PPR Gene
Tan-Trung Nguyen, Noelya Planchard, Jennifer Dahan, Nadège Arnal, Sandrine Balzergue, Abdelilah Benamar, Pierre Bertin, Véronique Brunaud, Céline Dargel-Graffin, David Macherel,et al.
Oxford University Press (OUP)
Abstract The high mutational load of mitochondrial genomes combined with their uniparental inheritance and high polyploidy favors the maintenance of deleterious mutations within populations. How cells compose and adapt to the accumulation of disadvantageous mitochondrial alleles remains unclear. Most harmful changes are likely corrected by purifying selection, however, the intimate collaboration between mitochondria- and nuclear-encoded gene products offers theoretical potential for compensatory adaptive changes. In plants, cytoplasmic male sterilities are known examples of nucleo-mitochondrial coadaptation situations in which nuclear-encoded restorer of fertility (Rf) genes evolve to counteract the effect of mitochondria-encoded cytoplasmic male sterility (CMS) genes and restore fertility. Most cloned Rfs belong to a small monophyletic group, comprising 26 pentatricopeptide repeat genes in Arabidopsis, called Rf-like (RFL). In this analysis, we explored the functional diversity of RFL genes in Arabidopsis and found that the RFL8 gene is not related to CMS suppression but essential for plant embryo development. In vitro-rescued rfl8 plantlets are deficient in the production of the mitochondrial heme–lyase complex. A complete ensemble of molecular and genetic analyses allowed us to demonstrate that the RFL8 gene has been selected to permit the translation of the mitochondrial ccmFN2 gene encoding a heme–lyase complex subunit which derives from the split of the ccmFN gene, specifically in Brassicaceae plants. This study represents thus a clear case of nuclear compensation to a lineage-specific mitochondrial genomic rearrangement in plants and demonstrates that RFL genes can be selected in response to other mitochondrial deviancies than CMS suppression.

Saccharomyces cerevisiae, a powerful model for studying rRNA modifications and their effects on translation fidelity
Agnès Baudin-Baillieu and Olivier Namy
MDPI AG
Ribosomal RNA is a major component of the ribosome. This RNA plays a crucial role in ribosome functioning by ensuring the formation of the peptide bond between amino acids and the accurate decoding of the genetic code. The rRNA carries many chemical modifications that participate in its maturation, the formation of the ribosome and its functioning. In this review, we present the different modifications and how they are deposited on the rRNA. We also describe the most recent results showing that the modified positions are not 100% modified, which creates a heterogeneous population of ribosomes. This gave rise to the concept of specialized ribosomes that we discuss. The knowledge accumulated in the yeast Saccharomyces cerevisiae is very helpful to better understand the role of rRNA modifications in humans, especially in ribosomopathies.

Translational accuracy of a tethered ribosome
Celine Fabret and Olivier Namy
Oxford University Press (OUP)
Abstract Ribosomes are evolutionary conserved ribonucleoprotein complexes that function as two separate subunits in all kingdoms. During translation initiation, the two subunits assemble to form the mature ribosome, which is responsible for translating the messenger RNA. When the ribosome reaches a stop codon, release factors promote translation termination and peptide release, and recycling factors then dissociate the two subunits, ready for use in a new round of translation. A tethered ribosome, called Ribo-T, in which the two subunits are covalently linked to form a single entity, was recently described in Escherichia coli. A hybrid ribosomal RNA (rRNA) consisting of both the small and large subunit rRNA sequences was engineered. The ribosome with inseparable subunits generated in this way was shown to be functional and to sustain cell growth. Here, we investigated the translational properties of Ribo-T. We analyzed its behavior during amino acid misincorporation, −1 or +1 frameshifting, stop codon readthrough, and internal translation initiation. Our data indicate that covalent attachment of the two subunits modifies the properties of the ribosome, altering its ability to initiate and terminate translation correctly.

Increased expression of tryptophan and tyrosine tRNAs elevates stop codon readthrough of reporter systems in human cell lines
Petra Beznosková, Laure Bidou, Olivier Namy, and Leoš Shivaya Valášek
Oxford University Press (OUP)
Abstract Regulation of translation via stop codon readthrough (SC-RT) expands not only tissue-specific but also viral proteomes in humans and, therefore, represents an important subject of study. Understanding this mechanism and all involved players is critical also from a point of view of prospective medical therapies of hereditary diseases caused by a premature termination codon. tRNAs were considered for a long time to be just passive players delivering amino acid residues according to the genetic code to ribosomes without any active regulatory roles. In contrast, our recent yeast work identified several endogenous tRNAs implicated in the regulation of SC-RT. Swiftly emerging studies of human tRNA-ome also advocate that tRNAs have unprecedented regulatory potential. Here, we developed a universal U6 promotor-based system expressing various human endogenous tRNA iso-decoders to study consequences of their increased dosage on SC-RT employing various reporter systems in vivo. This system combined with siRNA-mediated downregulations of selected aminoacyl-tRNA synthetases demonstrated that changing levels of human tryptophan and tyrosine tRNAs do modulate efficiency of SC-RT. Overall, our results suggest that tissue-to-tissue specific levels of selected near-cognate tRNAs may have a vital potential to fine-tune the final landscape of the human proteome, as well as that of its viral pathogens.

Pharmacological Premature Termination Codon Readthrough of ABCB11 in Bile Salt Export Pump Deficiency: An In Vitro Study
Rachida Amzal, Alice Thébaut, Martine Lapalus, Marion Almes, Brigitte Grosse, Elodie Mareux, Mauricette Collado‐Hilly, Anne Davit‐Spraul, Laure Bidou, Olivier Namy,et al.
Wiley
Progressive familial intrahepatic cholestasis type 2 (PFIC2) is a severe hepatocellular cholestasis due to biallelic mutations in ABCB11 encoding the canalicular bile salt export pump (BSEP). Nonsense mutations are responsible for the most severe phenotypes. The aim was to assess the ability of drugs to induce readthrough of six nonsense mutations (p.Y354X, p.R415X, p.R470X, p.R1057X, p.R1090X, and p.E1302X) identified in patients with PFIC2.

RiboDoc: A Docker-based package for ribosome profiling analysis
Pauline François, Hugo Arbes, Stéphane Demais, Agnès Baudin-Baillieu, and Olivier Namy
Elsevier BV

Divergent effects of translation termination factor eRF3A and nonsense-mediated mRNA decay factor UPF1 on the expression of uORF carrying mRNAs and ribosome protein genes
Affaf Aliouat, Isabelle Hatin, Pierre Bertin, Pauline François, Vérène Stierlé, Olivier Namy, Samia Salhi, and Olivier Jean-Jean
Informa UK Limited
ABSTRACT In addition to its role in translation termination, eRF3A has been implicated in the nonsense-mediated mRNA decay (NMD) pathway through its interaction with UPF1. NMD is a RNA quality control mechanism, which detects and degrades aberrant mRNAs as well as some normal transcripts including those that harbour upstream open reading frames in their 5ʹ leader sequence. In this study, we used RNA-sequencing and ribosome profiling to perform a genome wide analysis of the effect of either eRF3A or UPF1 depletion in human cells. Our bioinformatics analyses allow to delineate the features of the transcripts controlled by eRF3A and UPF1 and to compare the effect of each of these factors on gene expression. We find that eRF3A and UPF1 have very different impacts on the human transcriptome, less than 250 transcripts being targeted by both factors. We show that eRF3A depletion globally derepresses the expression of mRNAs containing translated uORFs while UPF1 knockdown derepresses only the mRNAs harbouring uORFs with an AUG codon in an optimal context for translation initiation. Finally, we also find that eRF3A and UPF1 have opposite effects on ribosome protein gene expression. Together, our results provide important elements for understanding the impact of translation termination and NMD on the human transcriptome and reveal novel determinants of ribosome biogenesis regulation.

Turnover of ribosome-associated transcripts from de novo ORFs produces gene-like characteristics available for de novo gene emergence in wild yeast populations
Éléonore Durand, Isabelle Gagnon-Arsenault, Johan Hallin, Isabelle Hatin, Alexandre K. Dubé, Lou Nielly-Thibault, Olivier Namy, and Christian R. Landry
Cold Spring Harbor Laboratory
Little is known about the rate of emergence of de novo genes, what their initial properties are, and how they spread in populations. We examined wild yeast populations (Saccharomyces paradoxus) to characterize the diversity and turnover of intergenic ORFs over short evolutionary timescales. We find that hundreds of intergenic ORFs show translation signatures similar to canonical genes, and we experimentally confirmed the translation of many of these ORFs in laboratory conditions using a reporter assay. Compared with canonical genes, intergenic ORFs have lower translation efficiency, which could imply a lack of optimization for translation or a mechanism to reduce their production cost. Translated intergenic ORFs also tend to have sequence properties that are generally close to those of random intergenic sequences. However, some of the very recent translated intergenic ORFs, which appeared <110 kya, already show gene-like characteristics, suggesting that the raw material for functional innovations could appear over short evolutionary timescales.

Methotrexit, a HeteroGenious cleaning factory
, William Briand, Ousmane Dao, Guillaume Garnier, Raphaël Guegan, Britany Marta, Clémence Maupu, Julie Miesch, Kenn Papadopoulo, Arthur Radoux,et al.
EDP Sciences
iGEM (pour international genetically engineered machine) est un concours international autour de la biologie synthétique réunissant des étudiants de toutes disciplines (mathématiques, physique, biologie, arts, etc.). « L’objectif est de construire un système biologique fonctionnel complexe, en assemblant des composants individuels moléculaires simples et standardisés (fragments d’ADN), appelés « briques biologiques » (biobriques), sorte de « legos » moléculaires, entreposés au MIT (Massachusetts Institute of Technology) (le registry of standard biological parts contient environ 20 000 biobriques). C’est une démarche proche de celle de l’ingénieur qui assemble des circuits électroniques ». En 2004, lors de sa création par le MIT (→), la compétition iGEM regroupait une quarantaine de projets ; 14 ans plus tard, elle accueille 350 équipes (6 000 étudiants, avec leurs instructeurs) issues des universités du monde entier. Elle culmine en un Giant Jamboree de quatre jours à Boston en novembre, au cours duquel les équipes présentent leur projet. Le « wiki » de la compétition (www.igem.org) présente l’ensemble des projets ainsi que le palmarès. Cette année, ont été décernées 114 médailles d’or, 68 d’argent et 107 de bronze. Neuf équipes françaises étaient engagées. (→) Voir l’article de J. Peccoud et L. Coulombel, dont certains passages sont repris dans ce « chapo », m/s n° 5, mai 2007, page 551

The translational landscape of Arabidopsis mitochondria
Noelya Planchard, Pierre Bertin, Martine Quadrado, Céline Dargel-Graffin, Isabelle Hatin, Olivier Namy, and Hakim Mireau
Oxford University Press (OUP)
Abstract Messenger RNA translation is a complex process that is still poorly understood in eukaryotic organelles like mitochondria. Growing evidence indicates though that mitochondrial translation differs from its bacterial counterpart in many key aspects. In this analysis, we have used ribosome profiling technology to generate a genome-wide snapshot view of mitochondrial translation in Arabidopsis. We show that, unlike in humans, most Arabidopsis mitochondrial ribosome footprints measure 27 and 28 bases. We also reveal that respiratory subunits encoding mRNAs show much higher ribosome association than other mitochondrial mRNAs, implying that they are translated at higher levels. Homogenous ribosome densities were generally detected within each respiratory complex except for complex V, where higher ribosome coverage corroborated with higher requirements for specific subunits. In complex I respiratory mutants, a reorganization of mitochondrial mRNAs ribosome association was detected involving increased ribosome densities for certain ribosomal protein encoding transcripts and a reduction in translation of a few complex V mRNAs. Taken together, our observations reveal that plant mitochondrial translation is a dynamic process and that translational control is important for gene expression in plant mitochondria. This study paves the way for future advances in the understanding translation in higher plant mitochondria.

Deciphering the reading of the genetic code by near-cognate tRNA
Sandra Blanchet, David Cornu, Isabelle Hatin, Henri Grosjean, Pierre Bertin, and Olivier Namy
Proceedings of the National Academy of Sciences
Significance Protein translation is a key cellular process in which each codon of mRNAs has to be accurately and efficiently recognized by cognate tRNAs of a large repertoire of noncognate tRNAs. A successful decoding process is largely dependent on the presence of modified nucleotides within the anticodon loop, especially of tRNAs having to read A/U-rich codons. In this latter case, their roles appear to stabilize the codon–anticodon interaction, allowing them to reach an optimal energetic value close to that of other interacting tRNAs involving G/C-rich anticodons. In this work we demonstrate that, while helping an efficient translation of A/U-rich codons, modified nucleotides also allow certain unconventional base pairing to occur, as evidenced in the case of stop codon suppression.

Factors influencing readthrough therapy for frequent cystic fibrosis premature termination codons
Iwona Pranke, Laure Bidou, Natacha Martin, Sandra Blanchet, Aurélie Hatton, Sabrina Karri, David Cornu, Bruno Costes, Benoit Chevalier, Danielle Tondelier,et al.
European Respiratory Society (ERS)
Premature termination codons (PTCs) are generally associated with severe forms of genetic diseases. Readthrough of in-frame PTCs using small molecules is a promising therapeutic approach. Nonetheless, the outcome of preclinical studies has been low and variable. Treatment efficacy depends on: 1) the level of drug-induced readthrough, 2) the amount of target transcripts, and 3) the activity of the recoded protein. The aim of the present study was to identify, in the cystic fibrosis transmembrane conductance regulator (CFTR) model, recoded channels from readthrough therapy that may be enhanced using CFTR modulators.First, drug-induced readthrough of 15 PTCs was measured using a dual reporter system under basal conditions and in response to gentamicin and negamycin. Secondly, exon skipping associated with these PTCs was evaluated with a minigene system. Finally, incorporated amino acids were identified by mass spectrometry and the function of the predicted recoded CFTR channels corresponding to these 15 PTCs was measured. Nonfunctional channels were subjected to CFTR-directed ivacaftor-lumacaftor treatments.The results demonstrated that CFTR modulators increased activity of recoded channels, which could also be confirmed in cells derived from a patient.In conclusion, this work will provide a framework to adapt treatments to the patient's genotype by identifying the most efficient molecule for each PTC and the recoded channels needing co-therapies to rescue channel function.

Olivier Namy

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Scopus Publications