About CNRS
Others web sites

  SnoRNA Database

Search on the CNRS web site




Laboratoire de Biologie Moléculaire Eucaryote

UMR 5099
Director: Pierre-Emmanuel Gleizes


The Laboratory of Eukaryotic Molecular Biology (LBME), a joint Université Paul Sabatier- CNRS unit (UMR 5099), is located on the University of Toulouse-Paul Sabatier campus in the IBCG building. The LBME is part of the Center for Integrative Biology in Toulouse (CBI Toulouse).

Research projects by the seven groups/teams of the LBME aim at understanding the mechanisms of genetic and epigenetic control of gene expression in eukaryotes. LBME activities evolve around two major themes:

  • The structural and functional characterization of nuclear and nucleolar ribonucleoprotein particles (pre-ribosomes, snoRNPs, scaRNPs, 7SK…)
  • Dynamics of chromosome structure and chromatin, in the context of gene transcription, homologous recombination and proliferation.

All projects are basic research and may elucidate the molecular basis of different pathologies including the Prader-Willi syndrome, the Blackfan-Diamond anemia, Dyskeratosis congenita and Cancer.

Research questions are addressed at different scales in a large number of model systems from single molecules to whole organisms (yeast, mouse and drosophila), including cell culture of primary or transformed cell lines. The LBME is leader in the study of nucleic acid/protein complexes using genetic, molecular biology, biochemistry, genomics, cell (fluorescence microscopy) and structural biology (cryo electronic microscopy) approaches.






Senior Post-doc positions

News Archives


    The nuclear pore complex is the gateway regulating exchanges between nucleus and cytoplasm. This transport machinery must allow a very high flow rate, but also effectively select macromolecules passing from one compartment to the other. In a study published in Nature Communications, the team of Pierre-Emmanuel Gleizes at the LBME-CBI, in collaboration with the CBI electron microscopy facility (METi) and Jean-Yves Dauxois at the Mathematical Institute of Toulouse, established the path followed by macromolecular particles, namely pre-ribosomes, in this nanoscale tunnel. For this, they used electron tomography, a 3-D electron microscopy technique. This study makes it possible to distinguish different stages of transport of pre-ribosomes through the nuclear pore complex and to precisely locate the selection barrier. In addition, the researchers were able to estimate the average dwell time of these particles in the nuclear pore on the basis of mathematical modeling.

    plusLearn more ...

  • The Npa1p complex chaperones the assembly of the earliest eukaryotic large ribosomal subunit precursor.

    Ribosomes, the molecular machines synthesizing proteins, are composed of a small and large subunit, each formed by the binding of numerous ribosomal proteins (RPs) to properly folded ribosomal RNAs (rRNAs). RP incorporation as well as processing and folding of rRNAs occur within a succession of precursor particles called the pre-ribosomal particles. Formation of the initial pre-60S particle, the first precursor to the large ribosomal subunit, is the least understood step of ribosome biogenesis in eukaryotes. This pre-ribosomal particle contains several assembly factors, including RNA helicases believed to catalyse key conformational rearrangements. Here, we show that the Dbp6p helicase, a component of the first pre-60S particle, associates with a complex of four assembly factors. The backbone of this complex is the Npa1 protein, which directly binds to Dbp6 and is required for its integration within pre-ribosomal particles. We show that Npa1p binds to sequences forming the core of large subunit rRNAs as well as small nucleolar RNAs required for chemical modification of large subunit rRNAs. Altogether our results suggest that the Npa1p complex plays a crucial role in the chemical modification and folding of large subunit rRNAs.


  • A new player of ribosome synthesis involved in dyskeratosis congenita

    Protein synthesis is performed by 5 to 10 millions of ribosomes in each human cell. These molecular machines are made of RNAs and proteins that are assembled following a complex and energy-consumming pathway. Defects in ribosome assembly are associated to various pathologies, including congenital diseases and cancers. A new study led Pierre-Emmanuel Gleizes and Marie-Françoise O’Donohue at LBME-CBI, in collaboration with the group of Ulrike Kutay at ETH-Zürich, now shows that PARN (Poly-A specific RiboNuclease), a 3’-5’ exonuclease mutated in dyskeratosis congenita and idiopathic pulmonary fibrosis, is an unexpected player of ribosome assembly. These new findings redefines PARN’s cellular function, which is mainly known for its role in mRNA turn-over, and enforce the hypothesis that a defect in ribosome synthesis could participate in the ethiology of dykeratosis congenita in some cases.

    plusLearn more ...

  • A new 7SK-containing RNP regulates RNA pol II transcription in a gene-specific fashion

    The 7SK small nuclear RNP (snRNP), composed of the 7SK snRNA, Larp7 and MePCE, controls the transcriptional stimulatory function of the Positive Transcription Elongation Factor b (P-TEFb) through sequestering active P-TEFb into large transcriptionally inactive 7SK/P-TEFb RNP. The team of Tamás Kiss at LBME, in collaboration with the team of Shona Murphy (University of Oxford), identified a new 7SK complex encompassing the 7SK snRNP and the recently identified RNA pol II-specific spliceosomal snRNA transcription factor, the Little Elongation Complex (LEC). The 7SK/LEC RNP specifically associates with pol II-specific snRNA genes to promote RNA pol II recruitment and elongation. Depletion of 7SK snRNP disrupts LEC integrity, prevents LEC accumulation in Cajal bodies where 7SK/LEC assembly likely occurs and eventually, inhibits snRNA synthesis. Thus, 7SK is a multifunctional transcriptional regulatory snRNP that, besides controlling the global level of active P-TEFb, also functions as a classical gene-specific transcription factor that promotes expression of pol II-specific sn/snoRNA genes. This work has been published in the EMBO Journal.

    plusLearn more ...

  • Functional link between Prp43 helicase activation and binding of the ATP base during eukaryotic ribosome biogenesis

    In eukaryotes, ribosome synthesis involves the assembly and maturation of large precursor particles, the pre-ribosomal particles, containing ribosomal RNA precursors, ribosomal proteins and numerous assembly and maturation factors. Among these factors, Prp43 belongs to the family of RNA helicases. Prp43 has the ability to hydrolyze ATP and modulate RNA-RNA interactions (helicase activity) and its function is controlled by protein co-factors containing so-called “G-patch domains”. In collaboration with Nicolas Leulliot (LCRB, Université Paris Descartes), we have identified Prp43 residues that interact directly with the base of the ATP molecule in the active site of the enzyme. A specific mutation abolishing this interaction inhibits the ATPase and helicase activities of Prp43 in vitro. This mutation induces defects in the maturation of the pre-ribosomal particles in yeast cells that are highly reminiscent of those induced by the inactivation of one of the G-patch co-factors of Prp43, the Gno1 protein. These data suggest that the pre-ribosomal particle maturation defects induced by this Prp43 mutation very likely result from an impaired activation of Prp43 by Gno1. This study reveals that the interaction between Prp43 residues and the ATP base are important for the activity and regulation of this family of helicases.


    plusLearn more ...

  • G4 hunting season is open

    Guanine rich sequences (G) are able to adopt secondary structures called Guanine quadruplexes (G4). G4-forming sequences are associated with telomere biology, replication origins and regulation of gene expression but also with genetically instable sites. So far, the search of such sequences was based on pattern matches. Together with Jean-Louis Mergny (IECB , Bordeaux) , Laurent Lacroix of the Cuvier team from the LBME has developed a new predictive tool for G4 - G4Hunter - which led to re-evaluate by a factor of 2 to 10 the G4 propensity of many genomes.


  • Mating type specific folding of yeast chromosome III revealed by mathematical modelling of 3 color 3D live cell imaging

    How variations in the three-dimensional organization of chromosomes are regulated is key to gain better understanding of genome function from gene expression to DNA repair and recombination. In an article published in PLoS Computational Biology in June 2015, the Bystricky group in collaboration with Alain Kamgoué, Mathematics/Informatics at the LBME/LMGM, developed original quantitative image analysis methods to determine chromosome conformation from relative positions of multiple fluorescently tagged DNA loci.


    plusLearn more ...

Imprimer Contact Plan du site Credits




Laboratoire de Biologie
Moléculaire Eucaryote
UMR 5099