Publications

2026

• Permuted 23S rRNA is integrated in 50S ribosome particles in Thermococcus barophilus
  
  • Gaspin Christine
  • Canal Isabelle
  • Capeyrou Régine
  • Da Cunha Violette
  • Bourgeois Gabrielle
  • Madru Clément
  • Schmitt Emmanuelle
  • Clouet D’orval Béatrice
  • Kwapisz Marta
  • Bouvier Marie
  , 2026. ABSTRACT In Archaea, a prevalent class of circular RNAs corresponds to 16S and 23S ribosomal RNA intermediates (circ-pre-rRNAs). A conserved bulge-helix-bulge (BHB) motif within the 16S and 23S rRNAs processing stems and adjacent to the circularization site in Euryarchaeota and TACK superphylum suggests that pre-rRNAs circularization is widely conserved across Archaea. Using genome-wide transcriptomic data obtained on total RNAs of wild-type Thermococcus barophilus cells, we recovered the canonical circularization junctions of the 16S and 23S circ-pre-rRNAs at the predicted BHB motifs. We also identified three alternatives 23S circular junctions introducing variability at the 3’ end of the mature rRNA. We investigated the different forms of 16S and 23S by performing primer extension and RACE experiments. We showed that while the 16S rRNA has standard 5’ and 3’ extremities, the main form of 23S rRNA is circularly permuted, with helix H99 now at its 5’ end. This permutation most probably emerged from the deletion of helix H98 from the 23S circ-pre-rRNA. Interestingly, we showed that the permuted 23S rRNA is incorporated into ribosome subunits and 70S monosomes. The significance of this event in generating functional 50S particles remains to be determined. (10.64898/2026.03.23.713588)
  DOI : 10.64898/2026.03.23.713588
• Guanosine 10 methylation by TRMT11–TRMT112 optimizes human mitochondrial tRNAs for efficient translation
  
  • Petrosyan Jonny
  • Yilmaz Mehmet
  • Scheitl Carolin
  • Lemus-Diaz Nicolas
  • Boshnakovska Angela
  • Tay Laurianne
  • Hu Wanwan
  • Beine-Golovchuk Olga
  • Touboul David
  • Richter-Dennerlein Ricarda
  • Höbartner Claudia
  • Graille Marc
  • Rehling Peter
  • Bohnsack Katherine
  Nucleic Acids Research, Oxford University Press, 2026, 54 (16), pp.gkag859. Modified nucleotides are essential determinants of RNA function, and identifying the enzymes that install them is fundamental to understanding their cellular roles. Here, we show that the human RNA methyltransferase TRMT11 and its cofactor TRMT112 are imported into mitochondria via N-terminal targeting signals. Using a recently developed N2-methylguanosine (m2G)-sensitive DNAzyme, we demonstrate that TRMT11 catalytic activity and interaction with TRMT112 are required for installation of m2G at position 10 in 13 mitochondrial (mt-)tRNAs. The crosslinking profile of TRMT11 on mt-tRNAs experimentally supports a model of the TRMT11–TRMT112–mt-tRNATrp complex in which the THUMP domain contacts the 3′ end of the acceptor stem, and G10 is flipped into the S-adenosylmethionine binding pocket for methylation. Transcriptome-wide mapping reveals that TRMT11 interacts with most nuclear-encoded and mt-tRNAs, but only methylates a subset. In vitro reconstitution of TRMT11–TRM112-mediated methylation defines key structural requirements for m2G10 installation across different mt-tRNAs, and reveals how pathogenic mutations influence this modification. TRMT11–TRMT112 recognizes folded mt-tRNAs, and in the degenerate mt-tRNALys, m1A9 strongly enhances m2G10 methylation efficiency. Loss of m2G10 modifications alters the conformation of numerous mt-tRNAs, perturbs mitochondrial protein synthesis, and impairs oxidative phosphorylation, highlighting an essential role of this modification in maintaining mitochondrial function. (10.1093/nar/gkag859)
  DOI : 10.1093/nar/gkag859
• Evolutionary Convergence on a Dihydrofolate Reductase Mutation Drives Trimethoprim–Sulfamethoxazole Resistance in Burkholderia thailandensis
  
  • Guillier Sophie
  • Lazennec-Schurdevin Christine
  • Mondange Lou
  • Sarilar Véronique
  • Marchandeau Mélissa
  • Lemoigne Chloé
  • Lamer Ombeline
  • Lescat Mathilde
  • Schmitt Emmanuelle
  • Mechulam Yves
  • Garrec Julian
  • Biot Fabrice
  ACS Infectious Diseases, American Chemical Society, 2026, 12 (8), pp.2627-2641. <div><p>Trimethoprim–sulfamethoxazole (SXT) remains central to melioidosis eradication therapy, yet the genetic basis of resistance evolution in Burkholderia pseudomallei is not fully defined. Using Burkholderia thailandensis as a biosafe surrogate, we subjected populations to stepwise in vitro evolution under increasing SXT concentrations. Whole-genome sequencing revealed rapid population diversification followed by selective sweeps leading to fixation of fitter resistant variants. Early adaptation involved mutations in regulators of RND efflux systems and folate-associated genes, consistent with multifactorial resistance. Despite this heterogeneity, all evolutionary trajectories converged on a single nonsynonymous substitution, I99L, in dihydrofolate reductase (DHFR/FolA), which rose to fixation at high SXT concentrations. This substitution mirrors changes reported in SXT-resistant B. pseudomallei isolates from chronic infections. Allelic reconstruction demonstrated that Bt-DHFR(I99L) is sufficient to confer a 4- to 16-fold increase in trimethoprim MIC. Biochemical and structural analyses showed preserved catalytic activity but reduced trimethoprim binding, consistent with an allosteric resistance mechanism. Together, these findings establish DHFR as a dominant evolutionary target under SXT pressure and support B. thailandensis as a robust model for dissecting resistance evolution in B. pseudomallei.</p></div> (10.1021/acsinfecdis.5c01132)
  DOI : 10.1021/acsinfecdis.5c01132
• The Nance-Horan syndrome protein NHS regulates cell migration persistence by organizing WAVE and N-WASP nucleation-promoting factor complexes
  
  • Tsydenzhapova Ekaterina
  • Fokin Artem
  • David Nicolas
  • Rocques Nathalie
  • Polesskaya Anna
  • Haddad Iman
  • Vinh Joëlle
  • Guérois Raphaël
  • Gautreau Alexis
  Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2026, pp.113443. The function of the NHS gene that is responsible for the Nance-Horan Syndrome has remained elusive at the cellular level. Using CRISPR/Cas9, we inactivated the NHS gene in MCF10A cells and characterized the isoforms expressed in these cells. NHS KO cells displayed reduced migration persistence, a phenotype that was fully rescued by the long isoform 1 (i1) that contains a N-terminal WAVE Homology Domain (WHD), but only partially rescued by the short isoform 2 (i2), which does not. Patient mutations resulting in NHS proteins truncated at their C-terminus also reduced the ability of NHS i1 to rescue migration persistence. Using Tandem Affinity Purification (TAP) of NHS i1 and mass spectrometry, we identified as major NHS partners, all subunits of the WAVE Regulatory Complex (WRC) except WAVE subunits themselves, indicating that the WHD of NHS assembles a WAVE Shell Complex (WSC). The Arp2/3 complex and the Nucleation Promoting Factor (NPF) WAVE that activates it are critical for migration persistence. To investigate the role of the NHS-containing WSC, we performed TAP of the ABI1 subunit in parental and NHS KO cells and identified differential partners associated with ABI1 only in parental cells, but not in NHS KO cells. The most abundant of these were the WIPF2/N-WASP complex, which together with the kinase ABL2, was also critical for migration persistence. These results suggest that NHS controls cell migration by remodeling NPF complexes and their higher order assembly. (10.1016/j.jbc.2026.113443)
  DOI : 10.1016/j.jbc.2026.113443
• A family of ribosome hibernation factors widespread in Archaea
  
  • Madru Clément
  • Bourgeois Gabrielle
  • Dulermo Rémi
  • Capeyrou Régine
  • Joncour Gwendoline
  • Figuigui Karima
  • Duchateau Magalie
  • Chamot-Rooke Julia
  • Duboc Claire
  • L’haridon Stéphane
  • Mc Teer Logan
  • Kwapisz Marta
  • Clouet-D’orval Béatrice
  • Bouvier Marie
  • Mechulam Yves
  • Borrel Guillaume
  • Schmitt Emmanuelle
  • Flament Didier
  Nature Communications, Nature Publishing Group, 2026, 17 (1), pp.5751. Ribosome hibernation preserves translation machinery during stress, yet its mechanisms in Archaea remain poorly defined. Using cryo-EM analysis, we studied hibernation pathways in Pyrococcus abyssi stressed cells. We identified HibA, a previously unrecognized family of hibernation factors widespread in Archaea. HibA consists of a bacterial-like HPF/RaiA domain fused to a Cystathionine Beta Synthase module. Unexpectedly, HibA binds to the ribosome in three different conformations, occupying the A, P and E sites of tRNAs, as well as that of mRNA, enhancing its ability to protect the ribosome from degradation. Idle ribosomes also frequently accumulate the archaeal homolog of eukaryotic ribosome maturation protein SBDS (aSBDS), suggesting that stressed archaeal cells may engage parallel hibernation routes in which aSBDS can complement HibA. Deletion of hibA in Thermococcus barophilus delays recovery from stationary phase and reduces 70S ribosome pools, establishing its role in ribosome preservation. Taxonomic profiling shows that many archaeal lineages encode distinct repertoires of ribosome-associated protection factors, underscoring the modular and multi-layered nature of archaeal hibernation systems. In addition, a comprehensive phylogenetic analysis highlights the evolutionary relationships between prevalent ribosome hibernation factors across Bacteria and Archaea. (10.1038/s41467-026-72341-8)
  DOI : 10.1038/s41467-026-72341-8
• D-LIM: A neural network for interpretable gene–gene interactions
  
  • Wang Shuhui
  • Allauzen Alexandre
  • Nghe Philippe
  • Opuu Vaitea
  PLoS Computational Biology, PLOS, 2026. <div><p>Recent advances in gene editing can produce large genotype-fitness maps for targeted genes, yet predicting the effects of mutations between genes remains challenging. Indeed, biochemical models require knowledge of underlying parameters and interactions, whereas machine learning methods typically lack interpretability, as they do not link model parameters to biological quantities. We introduce D-LIM, a neural network that infers low-dimensional fitness landscapes directly from mutation-fitness data. The distinctive feature of D-LIM is that it assumes genes act through independent gene-specific molecular phenotypes whose nonlinear interactions determine fitness. When this assumption holds, the model yields accurate predictions and interpretable effective phenotypes. Conversely, failure reveals that a low-dimensional model is insufficient. Applied to deep mutational scanning of metabolic pathways, protein-protein interactions, and yeast environmental adaptation, D-LIM achieves state-ofthe-art predictive accuracy. The inferred phenotype-fitness landscapes reveal whether epistatic interactions can be captured by a low-dimensional continuous model and identify potential trade-offs. Moreover, D-LIM estimates mutational effects on the effective phenotypes, enabling weak extrapolation beyond the training domain. D-LIM demonstrates how simple structure constraints in a neural network can help inference and hypothesis generation in biology.</p></div>
• Autocatalytic cores in the diluted regime: classification and properties
  
  • Nandan Praneet
  • Nghe Philippe
  • Unterberger Jérémie
  Journal of Mathematical Biology, Springer, 2026, 92 (3), pp.36. Autocatalysis underlies the ability of chemical and biochemical systems to replicate. Autocatalysis was recently defined stoichiometrically for reaction networks; five types of minimal autocatalytic networks, termed autocatalytic cores were identified. A necessary and sufficient stoichiometric criterion was later established for dynamical autocatalysis in diluted regimes, ensuring a positive growth rate of autocatalytic species starting from infinitesimal concentrations, given that degradation rates are sufficiently low. Here, we show that minimal autocatalytic networks in the dynamical sense, in the diluted regime, follow the same classification as autocatalytic cores in the stoichiometric sense. We further prove the uniqueness of the stationary regimes of autocatalytic cores, with and without degradation, for all types, except types II with three catalytic loops or more, for which the question remains open. These results indicate that the stationary point is robust under perturbation at low concentrations. More complex behaviours require additional non-linear couplings. (10.1007/s00285-026-02357-7)
  DOI : 10.1007/s00285-026-02357-7
• Cold atmospheric plasma promotes migration persistence, through induced H2O2 and electric field
  
  • Labérie Benjamin
  • Saugé Louis
  • Polesskaya Anna
  • Rousseau Antoine
  • Gautreau Alexis M
  Biophysical Journal, Biophysical Society, 2026, 125 (3), pp.697-708. Cold atmospheric plasma (CAP) generates various products, including radiation, electrons, ions, an electric field, and reactive oxygen and nitrogen species. CAP promotes wound healing and has been implemented in several medical devices to treat acute or chronic wounds. Beyond the closure of the epidermal monolayer of keratinocytes, wound healing requires migration of dermal fibroblasts. The effect of CAP on fibroblast migration has been insufficiently characterized. Here, we show, using primary human dermal fibroblasts, that a 10-s exposure to CAP suffices to increase Arp2/3-dependent lamellipodium formation and migration persistence for several hours. In an attempt to identify the specific CAP-generated products involved in this activity, we found that reactive oxygen species and the electric field induced by plasma were critical for enhanced and sustained migration persistence. Taken separately, these two stimuli were only partially active in inducing migration persistence at the dose that CAP generates. However, their combination was sufficient to recapitulate the full enhancement of migration persistence obtained with CAP exposure, indicating that these two stimuli act in synergy and that they likely represent the active components of CAP to activate migration of dermal fibroblasts during wound healing. (10.1016/j.bpj.2025.11.2685)
  DOI : 10.1016/j.bpj.2025.11.2685
• Biochemical insights into the conserved interactions of NMD factors from budding yeast to humans
  
  • Ruiz-Gutierrez Nadia
  • Graille Marc
  • Le Hir Hervé
  • Saveanu Cosmin
  , 2026. Nonsense-mediated mRNA decay (NMD) is one of the most extensively studied pathways of cytoplasmic mRNA degradation. It plays a critical role in diverse cellular processes by eliminating aberrant transcripts containing premature stop codons and by regulating the stability of physiological mRNAs. NMD factors were initially identified through genetic screens in S. cerevisiae (UPF1, 2, 3) and C. elegans (SMG-1, SMG5-7). Subsequent biochemical studies revealed the composition of NMD complexes and identified additional factors. A major protein hub for NMD is Upf1, an ATP-dependent RNA helicase that is part of two mutually exclusive NMD assemblies, the Upf1-Upf2-Upf3 complex and the Upf1-decapping complex, which contains the decapping enzyme and its co-factors. Here, we discuss recent findings, primarily from budding yeast, on the protein-protein interactions driving NMD complex dynamics and their similarities to human NMD. Together, the N-terminal cysteine and histidine rich (CH) and helicase domains (HD) of Upf1 act as a hub for binding multiple partners. Upf1 is required for binding to NMD substrates and for the initiation of RNA degradation through decapping (yeast) or endonucleolytic hydrolysis (humans). We focus on the interplay between Upf2, Dcp2 and Nmd4 (yeast SMG6), which ensures the mutually exclusive formation of Upf1-bound subcomplexes modulating Upf1's affinity for RNA. Thus, the study of NMD factors interactions in different organisms sheds new light on the remarkable conservation of NMD molecular mechanisms.
• Deux nouveaux acteurs de la libération contrôlée des vésicules extracellulaires
  
  • Bizingre Chloé
  • Picard Flavien
  • Alleaume-Butaux Aurélie
  • Pietri Mathéa
  • Baudry Anne
  • Schneider Benoit
  Médecine/Sciences, EDP Sciences, 2026, 42 (1), pp.25-28. (10.1051/medsci/2025245)
  DOI : 10.1051/medsci/2025245
• The Logic of Proof of Concept Research
  
  • Malaterre Christophe
  • Nghe Philippe
  Mind, Oxford University Press (OUP), 2026. Proof of Concept Research (PoCR) is a prevalent facet of scientific inquiry, yet its epistemic features remain poorly understood. While novelty has been highlighted as a key characteristic, projectability—understood as the likelihood of being applicable to a broader range of contexts—is another. This study endeavours to construct a formal model that elucidates the implicit ampliative reasoning inherent in PoCR. Our model hinges on probability assumptions for target objects to simultaneously exhibit three properties: one that is a defining characteristic of these target objects; a second that is desired of them and whose demonstration is the empirical aim of PoCR; and a third that is promised in the background. Depending on assumptions about when these properties jointly obtain, we delineate paradigmatic, alternative, and tangential modes of reasoning. This classification and associated decision tree unveil distinct argumentative strategies that, despite not being deductively valid, may be employed to motivate PoCR and justify subsequent inferences upon successful proof of concept demonstration. The model and decision tree together provide a framework with which to better understand the general structure of widely used inferences in PoCR, and with which researchers and evaluators can more precisely design and assess PoCR projects. (10.1093/mind/fzaf051)
  DOI : 10.1093/mind/fzaf051
• 2′-O-methylation-dependent installation of N2-methylguanosine in the U6 internal stem loop facilitates efficient spliceosome assembly
  
  • Kleiber Nicole
  • Petrosyan Jonny
  • Greve Maria
  • Thomé Chairini C
  • Dybkov Olexandr
  • Tay Laurianne L E
  • Welp Luisa M
  • Hackert Philipp
  • Touboul David
  • Stark Holger
  • Bohnsack Markus T
  • Urlaub Henning
  • Herzel Lydia
  • Graille Marc
  • Höbartner Claudia
  • Bohnsack Katherine E
  Nature Communications, Nature Publishing Group, 2026, 17, pp.3793. The internal stem loop (ISL) of the human U6 snRNA, which catalyzes pre-mRNA splicing, contains LARP7-dependent, snoRNA-guided 2′-O-methylations and an N2-methylguanosine (m2G) that is required for splicing of weak splice sites. Here, we show that installation of m2G72 by the THUMPD2-TRMT112 methyltransferase complex is one of the last maturation events during U6 snRNP biogenesis. We dissect features of THUMPD2 required for association with U6 and present an experimentally validated model of the THUMPD2-TRMT112-U6 complex. Using in vitro methylation assays as well as a newly developed m2G-sensitive deoxyribozyme to monitor U6-m2G72 levels in cellular RNAs, we reveal that 2′-O-methylations within the U6 ISL enhance methylation of G72. We show that m2G72 and the 2′-O-methylations in U6 independently and interdependently influence alternative splicing. Furthermore, our data demonstrate that 2′-O-methylations in the ISL are required for incorporation of U6 into snRNPs whereas m2G72 influences the progression of the U6 snRNP into larger assemblies, highlighting distinct roles of these modifications during spliceosome assembly. (10.1038/s41467-026-72355-2)
  DOI : 10.1038/s41467-026-72355-2