A5080206459- Nuclear Structure and Function
- RNA Research and Splicing
- Microtubule and mitosis dynamics
- Ubiquitin and proteasome pathways
- Genetics, Aging, and Longevity in Model Organisms
- RNA modifications and cancer
- Endoplasmic Reticulum Stress and Disease
- RNA regulation and disease
- DNA Repair Mechanisms
- Autophagy in Disease and Therapy
- Viral Infections and Immunology Research
- Virus-based gene therapy research
- Genomics and Chromatin Dynamics
- Mitochondrial Function and Pathology
- Biochemical and Molecular Research
- RNA Interference and Gene Delivery
- Plant Molecular Biology Research
- Photosynthetic Processes and Mechanisms
- Chromosomal and Genetic Variations
- Fungal and yeast genetics research
- Enzyme Structure and Function
- Cell death mechanisms and regulation
- CRISPR and Genetic Engineering
- Genetics and Neurodevelopmental Disorders
Centre National de la Recherche Scientifique
2003-2025
Institut Jacques Monod
2010-2025
La Ligue Contre le Cancer
2023-2025
Université Paris Cité
2001-2024
Sorbonne Paris Cité
2014
Sorbonne Université
2001-2006
Institut Curie
1997-2000
Institut Pasteur
1997
Chromosome maintenance region 1 (CRM1), a protein that shares sequence similarities with the karyopherin β family of proteins involved in nuclear import pathway, was shown to form complex leucine-rich export signal (NES). This interaction inhibited by leptomycin B, drug prevents function CRM1 yeast. To analyze role CRM1-NES export, transport assay based on semipermeabilized cells developed. In this system, which reconstituted NES-, cytosol-, and energy-dependent B specifically blocked...
The adenovirus VA1 RNA (VA1), a 160-nucleotide (nt)-long transcribed by polymerase III, is efficiently exported from the nucleus to cytoplasm of infected cells, where it antagonizes interferon-induced antiviral defense system. We recently reported that nuclear export mediated cis-acting motif, called minihelix, comprises double-stranded stem (>14 nt) with base-paired 5' end and 3-8-nt protruding 3' end. minihelix motif Ran-dependent, which indicates involvement karyopherin-related factor...
The mRNA nuclear export receptor Mex67/Mtr2 is recruited to mRNAs through RNA-binding adaptors, including components of the THO/TREX complex that couple transcription export. Here we show ubiquitin-associated (UBA) domain Mex67 not only required for proper but also contributes recruitment transcribing genes. Our results reveal UBA directly interacts with polyubiquitin chains and Hpr1, a component complex, which regulated by ubiquitylation in transcription-dependent manner. This interaction...
Autophagy, the process by which proteins or organelles are engulfed autophagosomes and delivered for vacuolar/lysosomal degradation, is induced to ensure survival under starvation other stresses. A selective autophagic pathway 60S ribosomal subunits elicited nitrogen in yeast—ribophagy—was recently described requires Ubp3-Bre5 deubiquitylating enzyme. This discovery implied that an E3 ligases act upstream, whether inhibiting providing initial required signal. In this paper, we show...
MAST-like, or Greatwall (Gwl), an atypical protein kinase related to the evolutionarily conserved MAST family, is crucial for cell cycle control during mitotic entry. Mechanistically, activated by Cyclin B-Cdk1 phosphorylation of a 550 amino acids-long insertion in its activation segment. Subsequently, Gwl phosphorylates Endosulfine and Arpp19 convert them into inhibitors PP2A-B55 phosphatase, thereby preventing early dephosphorylation M-phase targets B-Cdk1. Here, searching elusive Gwl-like...
The karyopherin-related nuclear transport factor exportin-5 preferentially recognizes and transports RNAs containing minihelix motif, a structural cis-acting export element that comprises double-stranded stem (>14 nucleotides) with base-paired 5' end 3-8-nucleotide protruding 3' end. This motif is present in various small cellular viral polymerase III transcripts such as the adenovirus VA1 RNA (VA1). Here we show RNA-binding protein, ILF3 (interleukin enhancer binding 3) binds motif. Gel...
Life of sexually reproducing organisms starts with the fusion haploid egg and sperm gametes to form genome a new diploid organism. Using newly fertilized Caenorhabditis elegans zygote, we show that mitotic Polo-like kinase PLK-1 phosphorylates lamin LMN-1 promote timely lamina disassembly subsequent merging parental genomes into single nucleus after mitosis. Expression non-phosphorylatable versions LMN-1, which affect depolymerization during mitosis, is sufficient prevent mixing chromosomes...
Soluble factors are required to mediate nuclear export of protein and RNA through the pore complex (NPC). These soluble include receptors that bind directly transport substrate regulators determine assembly state receptor-substrate complexes. We recently reported identification NXT1, an NTF2-related factor stimulates in permeabilized cells undergoes nucleocytoplasmic shuttling vivo (Black, B.E., L. Lévesque, J.M. Holaska, T.C. Wood, B.M. Paschal. 1999. Mol. Cell. Biol. 19:8616-8624). Here,...
The nuclear envelope, which protects and organizes the genome, is dismantled during mitosis. In Caenorhabditis elegans zygote, envelope breakdown (NEBD) of parental pronuclei spatially temporally regulated mitosis to promote unification maternal paternal genomes. Nuclear pore complex (NPC) disassembly a decisive step NEBD, essential for permeabilization. By combining live imaging, biochemistry, phosphoproteomics, we show that NPC stepwise process involves Polo-like kinase 1 (PLK-1)-dependent...
To better characterize the mechanisms responsible for RNA export from nucleus, we developed an in vitro assay based on use of permeabilized HeLa cells. This new supports nuclear U1 snRNA, tRNA, and mRNA energy- Xenopusextract-dependent manner. snRNA requires a 5′ monomethylated cap structure, signal receptor CRM1, small GTPase Ran. In contrast, does not require participation CRM1. We show here that NXT1, NTF2-related protein binds directly to RanGTP, strongly stimulates mRNA. The ability...
Previously, we reported that the Polo-like kinase PLK-1 phosphorylates single Caenorhabditis elegans lamin (LMN-1) to trigger lamina depolymerization during mitosis. We showed this event is required form a pronuclear envelope scission removes membranes on juxtaposed oocyte and sperm envelopes in zygote, allowing parental chromosomes merge nucleus after segregation (Velez-Aguilera et al., 2020). Here, show cortical microtubule pulling forces contribute by promoting mitotic spindle elongation,...
The Bre5 protein is a cofactor for the deubiquitinating enzyme Ubp3, and it contains nuclear transfer factor 2 (NTF2)-like recognition module that essential Ubp3 activity. In this study, we report x-ray crystal structure of NTF2-like domain show forms homodimeric similar to other domains, except presence an intermolecular disulfide bond in crystals. Sedimentation equilibrium studies reveal under non-reducing conditions, exclusively dimeric, whereas bond-deficient mutant undergoes...
The nuclear envelope, which protects and organizes the interphase genome, is dismantled during mitosis. In C. elegans zygote, envelope breakdown (NEBD) of parental pronuclei spatially temporally regulated mitosis to promote unification genomes. During NEBD, Nuclear Pore Complex (NPC) disassembly critical for rupturing permeability barrier removing NPCs from membranes near centrosomes between juxtaposed pronuclei. By combining live imaging, biochemistry, phosphoproteomics, we characterized...
Abstract Cullin-RING E3-Ligases (CRLs), the largest family of E3 ubiquitin-Ligases, regulate diverse cellular processes by promoting ubiquitination target proteins. The evolutionarily conserved Leucine Rich Repeat protein 1 (LRR-1) is a substrate-recognition subunit CRL2LRR-1 E3-ligase. Here we provide genetic evidence supporting role this E3-enzyme in maintenance DNA replication integrity Caenorhabditis elegans. Through RNAi-based suppressor screens lrr-1(0) and cul-2(or209ts) mutants,...