A5078854007- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- RNA Research and Splicing
- Monoclonal and Polyclonal Antibodies Research
- Genomics and Phylogenetic Studies
- Genomics and Chromatin Dynamics
- Viral Infections and Immunology Research
- SARS-CoV-2 and COVID-19 Research
- Bacterial Genetics and Biotechnology
- RNA Interference and Gene Delivery
- Hepatitis C virus research
- Research on Leishmaniasis Studies
- Selenium in Biological Systems
- Bacteriophages and microbial interactions
- Viral gastroenteritis research and epidemiology
- Protein purification and stability
- Plant Virus Research Studies
- Invertebrate Immune Response Mechanisms
- Enzyme Production and Characterization
- Hematological disorders and diagnostics
- CRISPR and Genetic Engineering
- Glycosylation and Glycoproteins Research
- RNA regulation and disease
- Trypanosoma species research and implications
- Enzyme Catalysis and Immobilization
Université de Strasbourg
2016-2025
Centre National de la Recherche Scientifique
2014-2025
Inserm
2004-2025
Institut de génétique et de biologie moléculaire et cellulaire
2004-2025
Architecture et Réactivité de l'arN
2015-2024
Institut de Biologie Moléculaire et Cellulaire
2015-2024
Centre National pour la Recherche Scientifique et Technique (CNRST)
2023
GlaxoSmithKline (France)
2018-2020
GlaxoSmithKline (Netherlands)
2020
Dompé (Italy)
2005-2011
SARS-CoV-2 coronavirus is responsible for Covid-19 pandemic. In the early phase of infection, single-strand positive RNA genome translated into non-structural proteins (NSP). One first produced during viral NSP1, binds to host ribosome and blocks mRNA entry channel. This triggers translation inhibition cellular translation. spite presence NSP1 on ribosome, proceeds however. The molecular mechanism so-called evasion remains elusive. Here, we confirm that maintained in NSP1. NSP1-inhibition...
The SARS-CoV-2, a positive-sense single-stranded RNA Coronavirus, is global threat to human health. Thus, understanding its life cycle mechanistically would be important facilitate the design of antiviral drugs. A key aspect viral progression synthesis proteins by ribosome host. In Coronaviruses, this process regulated 5' and 3' untranslated regions (UTRs), but precise regulatory mechanism has not yet been well understood. particular, 5'-UTR genome most likely involved in translation...
The chemokine CXC ligand 8 (CXCL8)/IL-8 and related agonists recruit activate polymorphonuclear cells by binding the receptor 1 (CXCR1) CXCR2. Here we characterize unique mode of action a small-molecule inhibitor (Repertaxin) CXCR1 Structural biochemical data are consistent with noncompetitive allosteric interaction between Repertaxin, which, locking in an inactive conformation, prevents signaling. Repertaxin is effective cell recruitment vivo protects organs against reperfusion injury....
Abstract Expansion of G 4 C 2 repeats in the C9ORF72 gene is most prevalent inherited form amyotrophic lateral sclerosis and frontotemporal dementia. Expanded transcripts undergo repeat-associated non-AUG (RAN) translation producing dipeptide repeat proteins from all reading frames. We determined cis -factors trans influencing human transcripts. operates through a 5′–3′ cap-dependent scanning mechanism, requiring CUG codon located upstream an initiator Met-tRNA Met i . Production poly-GA,...
Abstract Eukaryotic mRNAs often contain a Kozak sequence that helps tether the ribosome to AUG start codon. The mRNA of histone H4 ( h4 ) does not undergo classical scanning but has evolved specific tethering mechanism. cryo-EM structure rabbit complex with mouse shows forms folded, repressive at entry site on 40S subunit next tip helix 16 18S ribosomal RNA (rRNA). Toe-printing and mutational assays reveal an interaction exists between purine-rich in complementary UUUC h16. Together present...
Mammalian mRNAs are generated by complex and coordinated biogenesis pathways acquire 5′-end m7G caps that play fundamental roles in processing translation. Here we show several selenoprotein not recognized efficiently translation initiation factor eIF4E because they bear a hypermethylated cap. This cap modification is acquired via maturation pathway similar to of the small nucle(ol)ar RNAs (sn- snoRNAs). Our findings also establish trimethylguanosine synthase 1 (Tgs1) interacts with for...
Cricket paralysis virus (CrPV) is a dicistrovirus. Its positive-sense single-stranded RNA genome contains two internal ribosomal entry sites (IRESs). The 5' untranslated region (5'UTR) IRES5'UTR mediates translation of non-structural proteins encoded by ORF1 whereas the well-known intergenic (IGR) IRESIGR required for structural from open reading frame 2 in late phase infection. Concerted action both IRES essential host shut-off and viral translation. has been extensively studied, contrast...
The 5′UTR part of coronavirus genomes plays key roles in the viral replication cycle and translation mRNAs. first 75–80 nt, also called leader sequence, are identical for genomic mRNA subgenomic Recently, it was shown that cooperative actions a segment nonstructural protein NSP1 essential both inhibition host mRNAs specific Here, sequence analyses RNA have been done several coronaviruses, with special attention to betacoronaviruses. conclusions are: (i) precise molecular signatures can be...
Host defense against infections encompasses both resistance, which targets microorganisms for neutralization or elimination, and resilience/disease tolerance, allows the host to withstand/tolerate pathogens repair damages. In Drosophila, Toll signaling pathway is thought mediate resistance fungal by regulating secretion of antimicrobial peptides, potentially including Bomanins. We find that Aspergillus fumigatus kills Drosophila mutants without invasion because its dissemination blocked...
In severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the non-structural protein NSP1 inhibits translation of host mRNAs by binding to mRNA entry channel ribosome and, together with 5'-untranslated region (UTR) viral mRNAs, allows evasion that inhibition. Here, we show mediates endonucleolytic cleavages both and in 5'UTR, but different cleavage patterns. The first pattern is observed interspersed regularly close 5' cap (6-11 nt downstream cap). Those positions depend more on...
The HCV genome encodes, within the NS3 gene, a serine protease whose activity specifically cleaves viral polyprotein precursor. Proteolytic processing of precursor by proteinase is essential for virion maturation and designing specific inhibitors this as possible anti-viral agents desirable practical objective. With view to studying both function enzyme, we directed our interest towards engineering macromolecular catalytic activity. We describe here affinity-selection biochemical...
The leishmaniases are diseases that affect millions of people across the world, in particular visceral leishmaniasis (VL) which is fatal unless treated. Current standard care for VL suffers from multiple issues and there a limited pipeline new candidate drugs. As such, clear unmet medical need to identify treatments. This paper describes optimization phenotypic hit against Leishmania donovani, major causative organism VL. key challenges were balance solubility metabolic stability while...
Dysfunction of mitochondrial translation is an increasingly important molecular cause human disease, but structural defects ribosomal subunits are rare. We used next-generation sequencing to identify a homozygous variant in the small protein 14 (MRPS14, uS14m) patient manifesting with perinatal hypertrophic cardiomyopathy, growth retardation, muscle hypotonia, elevated lactate, dysmorphy and mental retardation. In skeletal fibroblasts from patient, there was biochemical deficiency complex IV...
Canonical translation initiation involves ribosomal scanning, but short 5' untranslated region (5'UTR) mRNAs are translated in a scanning-independent manner. The extent and mechanism of not fully understood. Here we report that 5'UTR constitute substantial fraction the translatome. Short enriched with TISU (translation initiator 5'UTR), 12-nucleotide element directing efficient translation. Comprehensive mutagenesis revealed each AUG codon-flanking nucleotide contributes to translational...
RNA interference (RNAi) mediated by the small interfering (siRNA) pathway is a major antiviral mechanism in insects. This triggered when double-stranded (dsRNA) produced during virus replication recognized Dicer-2, leading to formation of virus-derived siRNA duplexes. These siRNAs are loaded onto programmable nuclease Argonaute-2 (AGO2), with one strand serving as guide target and cleave fully complementary sequences viral RNAs. While generated from dsRNA, specific species targeted for...
Proteins of the BCL7 family (BCL7A, BCL7B, and BCL7C) are among most recently identified subunits mammalian SWI/SNF chromatin remodeler complex absent from unicellular version this complex. Their function in is unknown, very limited structural information available, despite fact that they mutated several cancer types, notably blood malignancies hence medically relevant. Here, using cryo-electron microscopy combination with biophysical biochemical approaches, we show BCL7A forms a stable,...
Abstract SARS-CoV-2 coronavirus is responsible for Covid-19 pandemic. In the early phase of infection, single-strand positive RNA genome translated into non-structural proteins (NSP). One first produced during viral NSP1, binds to host ribosome and blocks mRNA entry channel. This triggers translation inhibition cellular translation. spite presence NSP1 on ribosome, proceeds however. The molecular mechanism so-called evasion remains elusive. Here, we confirm that maintained in NSP1....