A5026251524- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- RNA Research and Splicing
- Genomics and Phylogenetic Studies
- Peptidase Inhibition and Analysis
- Cancer-related molecular mechanisms research
- Advanced biosensing and bioanalysis techniques
- Bacteriophages and microbial interactions
- Fungal and yeast genetics research
- Viral Infections and Immunology Research
- Cystic Fibrosis Research Advances
- Bacterial Genetics and Biotechnology
- DNA and Nucleic Acid Chemistry
- CRISPR and Genetic Engineering
- HIV Research and Treatment
- RNA Interference and Gene Delivery
- Prion Diseases and Protein Misfolding
- Molecular Biology Techniques and Applications
- Mitochondrial Function and Pathology
- Monoclonal and Polyclonal Antibodies Research
- Protein Structure and Dynamics
- Enzyme Structure and Function
- Chemical Synthesis and Analysis
- Amino Acid Enzymes and Metabolism
- interferon and immune responses
Institut de Biologie Intégrative de la Cellule
2016-2025
Université Paris-Saclay
2016-2025
Commissariat à l'Énergie Atomique et aux Énergies Alternatives
2015-2025
Centre National de la Recherche Scientifique
2016-2025
CEA Paris-Saclay
2017-2025
Université Paris-Sud
2011-2024
University of Exeter
2023-2024
Institut Curie
2023-2024
Cornell University
2023-2024
Weill Cornell Medicine
2023-2024
Significance Translational control is a cornerstone of gene-expression regulation in physiological and pathological contexts. The contribution nonribosomal factors, including messenger RNAs (mRNAs) mRNA-bound to translational have been extensively studied. Recently, the hypothesis ribosome-mediated emerged, which proposes that cells produce ribosomes different composition displaying properties. This work reveals ribosomal RNA 2′-O-methylation can be modulated human ribosomes, at key...
Abstract Stop codon readthrough may be promoted by the nucleotide environment or drugs. In such cases, ribosomes incorporate a natural suppressor tRNA at stop codon, leading to continuation of translation in same reading frame until next and resulting expression protein with new potential function. However, identity tRNAs involved remains unclear, precluding identification amino acids incorporated position. We established an vivo reporter system for identifying mass spectrometry yeast...
The universal tRNA modification t6A is found at position 37 of nearly all tRNAs decoding ANN codons. absence t6A37 leads to severe growth defects in baker's yeast, phenotypes similar those caused by mcm5s2U34 synthesis. Mutants can be suppressed overexpression tRNALysUUU, but we show could not expressing any individual tRNA, and mcm5s2U are determinants for each other's formation. Our results suggest that deficiency, like protein folding defects, the led stress sensitivities (heat, ethanol,...
The development of ribosomal profiling (Riboseq) revealed the immense coding capacity human and viral genomes. Here, we used Riboseq to delineate translatome HIV-1 in infected CD4+ T cells. In addition canonical protein sequences (CDSs), identify 98 alternative open reading frames (ARFs), corresponding small Open Reading Frames (sORFs) that are distributed across HIV genome including UTR regions. Using a database genomes, observe most ARF amino-acid likely conserved among clade B C HIV-1,...
Human immunodeficiency virus type-1 (HIV-1) is a complex retrovirus that relies on alternative splicing, translational, and post-translational mechanisms to produce over 15 functional proteins from its single ~10 kb transcriptional unit. Using ribosome profiling, nascent protein labeling, RNA sequencing, whole-proteomics of infected CD4 + T lymphocytes, we characterized the transcriptional, landscape during infection. While viral infection exerts significant impact host transcript abundance,...
Nonsense mutations, generating premature termination codons (PTCs), account for 10% to 30% of the mutations in tumor suppressor genes. translational suppression, induced by small molecules including gentamicin and G418, has been suggested as a potential therapy counteract deleterious effects nonsense several genetic diseases cancers. We describe here that NB124, synthetic aminoglycoside derivative recently developed especially PTC strongly induces apoptosis human cells promoting high level...
We specifically sought genes within the yeast genome controlled by a non-conventional translation mechanism involving stop codon. For this reason, we designed computer program using database genomic regions, and seeking two adjacent open reading frames separated only unique codon (called SORFs). Among 58 SORFs identified, eight displayed bypass level ranging from 3 to 25%. each of sequences, demonstrated presence poly(A) mRNA. Using isogenic [PSI(+)] [psi(-)] strains, showed that for...
Summary The efficiency of translation termination in yeast can vary several 100‐fold, depending on the context around stop codon. We performed a computer analysis designed to identify open reading frames (ORFs) containing readthrough motif surrounding Eight ORFs were found display inefficient codon recognition, one which, PDE2 , encodes high‐affinity cAMP phosphodiesterase. demonstrate that Pde2p stability is very impaired by readthrough‐dependent extension protein. A 20‐fold increase was...
Prions are infectious proteins that can adopt a structural conformation is then propagated among other molecules of the same protein. [PSI+] an aggregated translational release factor eRF3. modifies cellular fitness, inducing various phenotypes depending on genetic background. However, genes displaying [PSI+]-controlled expression remain unknown. We used ribosome profiling in isogenic and [psi−] strains to identify changes induced by [PSI+]. found 100 with stop codon readthrough events...
Significance Protein translation is a key cellular process in which each codon of mRNAs has to be accurately and efficiently recognized by cognate tRNAs large repertoire noncognate tRNAs. A successful decoding largely dependent on the presence modified nucleotides within anticodon loop, especially having read A/U-rich codons. In this latter case, their roles appear stabilize codon–anticodon interaction, allowing them reach an optimal energetic value close that other interacting involving...
Little is known about the rate of emergence de novo genes, what their initial properties are, and how they spread in populations. We examined wild yeast populations ( Saccharomyces paradoxus ) to characterize diversity turnover intergenic ORFs over short evolutionary timescales. find that hundreds show translation signatures similar canonical we experimentally confirmed many these laboratory conditions using a reporter assay. Compared with have lower efficiency, which could imply lack...
Premature termination codons (PTCs) are generally associated with severe forms of genetic diseases. Readthrough in-frame PTCs using small molecules is a promising therapeutic approach. Nonetheless, the outcome preclinical studies has been low and variable. Treatment efficacy depends on: 1) level drug-induced readthrough, 2) amount target transcripts, 3) activity recoded protein. The aim present study was to identify, in cystic fibrosis transmembrane conductance regulator (CFTR) model,...
Messenger RNA translation is a complex process that still poorly understood in eukaryotic organelles like mitochondria. Growing evidence indicates though mitochondrial differs from its bacterial counterpart many key aspects. In this analysis, we have used ribosome profiling technology to generate genome-wide snapshot view of Arabidopsis. We show that, unlike humans, most Arabidopsis footprints measure 27 and 28 bases. also reveal respiratory subunits encoding mRNAs much higher association...
The noncoding genome plays an important role in de novo gene birth and the emergence of genetic novelty. Nevertheless, how sequences’ properties could promote novel genes shape evolution structural diversity proteins remains unclear. Therefore, by combining different bioinformatic approaches, we characterized fold potential amino acid sequences encoded all intergenic open reading frames (ORFs) S. cerevisiae with aim (1) exploring whether states’ proteomes is already present sequences, (2)...
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, Xrn1-sensitive (XUTs) are targeted by Nonsense-Mediated mRNA Decay (NMD), suggesting a translation-dependent degradation process. Here, we report that XUTs pervasively translated, which impacts their decay. We show globally accumulate upon elongation inhibition, but not...
Tgt is the enzyme modifying guanine (G) in tRNAs with GUN anticodon to queuosine (Q). tgt required for optimal growth of Vibrio cholerae presence sub-lethal aminoglycoside concentrations. We further explored here role Q34 efficiency codon decoding upon tobramycin exposure. characterized its impact on overall bacterial proteome, and elucidated molecular mechanisms underlying effects modification antibiotic translational stress response. Using reporters, we showed that impacts at tyrosine TAT...
The N6-methyladenosine (m6A) modification of HIV-1 RNAs plays an essential role in regulating viral infection. This has been widely studied but the number and precise positions m6A sites remain unclear due to lack precision detection methods. We used latest Nanopore chemistry direct base-calling option identify 18 m6As, 14 which were located at 3′ end genome, other four being central regions. Our data reveal differential methylation these between splicing isoforms. Eleven are clustered two...