A5011803721- DNA and Nucleic Acid Chemistry
- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- HIV Research and Treatment
- Cancer-related gene regulation
- RNA Research and Splicing
- Chemical Synthesis and Analysis
- HIV/AIDS drug development and treatment
- Biochemical and Molecular Research
- Mosquito-borne diseases and control
- CRISPR and Genetic Engineering
- Bacteriophages and microbial interactions
- interferon and immune responses
- Viral gastroenteritis research and epidemiology
- Respiratory viral infections research
- Cancer-related molecular mechanisms research
- Viral Infections and Outbreaks Research
- Viral Infections and Vectors
- Influenza Virus Research Studies
- Click Chemistry and Applications
- Epigenetics and DNA Methylation
- Insect symbiosis and bacterial influences
- Enzyme Structure and Function
Centre National de la Recherche Scientifique
2015-2024
Institut des Biomolécules Max Mousseron
2015-2024
École Nationale Supérieure de Chimie de Montpellier
2015-2024
Université de Montpellier
2015-2024
Bipar
2016-2018
Centre de Gestion Scientifique
2014
Alnylam Pharmaceuticals (United States)
2010
GTx (United States)
2010
Laboratoire de Chimie Organique
1991-2007
Centre de Recherche en Biologie cellulaire de Montpellier
1997
Abstract Cancer stem cells (CSCs) are a small but critical cell population for cancer biology since they display inherent resistance to standard therapies and give rise metastases. Despite accruing evidence establishing link between deregulation of epitranscriptome-related players tumorigenic process, the role messenger RNA (mRNA) modifications in regulation CSC properties remains poorly understood. Here, we show that cytoplasmic pool fat mass obesity-associated protein (FTO) impedes...
ABSTRACT The Flavivirus Zika virus (ZIKV) is the causal agent of neurological disorders like microcephaly in newborns or Guillain-Barre syndrome. Its NS5 protein embeds a methyltransferase (MTase) domain involved formation viral mRNA cap. We investigated structural and functional properties ZIKV MTase. show that MTase can methylate RNA cap structures at N-7 position cap, 2′-O on ribose first nucleotide, yielding cap-1 structure. In addition, methylates internal adenosines substrates. crystal...
Cell growth is a complex process shaped by extensive and coordinated changes in gene expression. Among these the tightly regulated translation of family growth-related mRNAs defined 5' terminal oligopyrimidine (TOP) motif. TOP mRNA partly controlled via eukaryotic initiation factor 4F (eIF4F), that recognizes cap structure. Recent studies have also implicated La-related protein 1 (LARP1), which competes with eIF4F for binding to ends. However, it has remained controversial whether LARP1...
Enzymes involved in RNA capping of SARS-CoV-2 are essential for the stability viral RNA, translation mRNAs, and virus evasion from innate immunity, making them attractive targets antiviral agents. In this work, we focused on design synthesis nucleoside-derived inhibitors against nsp14 (N7-guanine)-methyltransferase (N7-MTase) that catalyzes transfer methyl group S-adenosyl-l-methionine (SAM) cofactor to N7-guanosine cap. Seven compounds out 39 SAM analogues showed remarkable double-digit...
Transcription start-site (TSS) selection and alternative promoter (AP) usage contribute to gene expression complexity but little is known about their impact on translation. Here we performed TSS mapping of the translatome following energy stress. Assessing contribution cap-proximal nucleotides, found dramatic effect translation only upon As eIF4E levels were reduced, determined its binding capped-RNAs with different initiating nucleotides lowest affinity 5'cytidine in correlation...
The dengue virus (DV) is an important human pathogen from the Flavivirus genus, whose genome- and antigenome RNAs start with strictly conserved sequence pppAG. RNA-dependent RNA polymerase (RdRp), a product of NS5 gene, initiates synthesis de novo, i.e., without use pre-existing primer. Very little known about mechanism this novo initiation how conservation starting adenosine achieved. domain NS5PolDV NS5, upon on viral templates, synthesizes mainly dinucleotide primers that are then...
The Middle East respiratory syndrome coronavirus (MERS-CoV) nonstructural protein 16 (nsp16) is an S-adenosyl-l-methionine (SAM)-dependent 2'-O-methyltransferase (2'-O-MTase) that thought to methylate the ribose 2'-OH of first transcribed nucleotide (N1) viral RNA cap structures. This 2'-O-MTase activity regulated by nsp10. 2'-O methylation prevents virus detection cell innate immunity mechanisms and translation inhibition interferon-stimulated IFIT-1 protein. To unravel regulation...
A novel methodology that disrupts the dogma "RNA synthesis is incompatible with a whole base-labile strategy" has been developed. In this strategy (see scheme), 2′-OH groups are protected by pivaloyloxymethyl groups, compatible standard protections for nucleobases and phosphates. Protecting removed in short two-step all-base procedure to afford RNA efficiently, rapidly, high purity without chain rupture or isomerization.
ABSTRACT Alphaviruses are known to possess a unique viral mRNA capping mechanism involving the nonstructural protein nsP1. This enzyme harbors methyltransferase (MTase) and nsP1 guanylylation (GT) activities catalyzing transfer of methyl group from S -adenosylmethionine (AdoMet) N7 position GTP molecule followed by formation an m 7 GMP-nsP1 adduct. Subsequent GMP onto 5′ end has not been demonstrated in vitro yet. Here we report biochemical characterization Venezuelan equine encephalitis...
The L protein of mononegaviruses harbours all catalytic activities for genome replication and transcription. It contains six conserved domains (CR-I to -VI; Fig. 1a). CR-III has been linked polymerase polyadenylation activity, CR-V mRNA capping CR-VI cap methylation. However, how these are choreographed is poorly understood. Here we present the 2.2-Å X-ray structure CR-VI+, a portion human Metapneumovirus consisting region at its C terminus, +domain. domain methyltransferase fold, which...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOligonucleosides: synthesis of a novel methylhydroxylamine-linked nucleoside dimer and its incorporation into antisense sequencesJean Jacques Vasseur, Francoise Debart, Yogesh S. Sanghvi, P. Dan CookCite this: J. Am. Chem. Soc. 1992, 114, 10, 4006–4007Publication Date (Print):May 1, 1992Publication History Published online1 May 2002Published inissue 1...
A robust, reproducible, and scalable method for the solid-phase synthesis of 5′-triphosphates DNA, RNA, their chemically modified analogues using 5′-H-phosphonate intermediates is described. 5′-Triphosphates oligonucleotides with varying lengths sequences containing different 5′-terminal nucleotides, without internal sugar-backbone modifications, were efficiently prepared as crude products or further purified by HPLC.
The 5' end of eukaryotic mRNA carries a N(7)-methylguanosine residue linked by 5'-5' triphosphate bond. This cap moiety ((7m)GpppN) is an essential RNA structural modification allowing its efficient translation, limiting degradation cellular exonucleases and avoiding recognition as "nonself" the innate immunity machinery. In vitro synthesis capped important bottleneck for many biological studies. Moreover, lack methods large amounts starting with specific 5'-end sequence have hampered...
Mononegaviruses, such as Ebola virus, encode an L (large) protein that bears all the catalytic activities for replication/transcription and RNA capping. The C-terminal conserved region VI (CRVI) of contains a K-D-K-E tetrad typical 2'O methyltransferases (MTase). In mononegaviruses, cap-MTase have been involved in methylation N7 cap structure. These play critical role viral life cycle ensures efficient mRNA translation hampers detection by host innate immunity. functional characterization...
Abstract RNA 2′O-methylation is a ‘self’ epitranscriptomic modification allowing discrimination between host and pathogen. Indeed, human immunodeficiency virus 1 (HIV-1) induces of its genome by recruiting the cellular FTSJ3 methyltransferase, thereby impairing detection RIG-like receptors. Here, we show that 2′O-methylations interfere with antiviral activity interferon-stimulated gene 20-kDa protein (ISG20). Biochemical experiments showed ISG20-mediated degradation 2′O-methylated pauses two...
SAH-derived bisubstrates of SARS-CoV-2 cap RNA N 7-methyltransferase were synthesized, and two adenosines with an -arylsulfonamide core attached by -ethylthioether linker proved to be effective inhibitors in the submicromolar range.