Fabrice Jossinet

Fabrice Jossinet
University of Strasbourg | UNISTRA · Institut de Biologie Moléculaire et Cellulaire (IBMC)

PhD in Molecular and Cellular Biology

About

44
Publications
14,357
Reads
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2,428
Citations
Introduction
Teacher, molecular biologist and bioinformatician. Beside the bioinformatics support for collaborative projects, i'm leading a research group interested in a better understanding of the infection process of the pathogenic yeast Candida glabrata. Our experimental strategy combines dual RNA-Seq in host-pathogen interactions, CRISPR-Cas9 engineering, comparative genomics, biological networks reconstruction and analysis.
Additional affiliations
September 2002 - present
University of Strasbourg
Position
  • Professor (Associate)
January 2002 - April 2002
Rutgers, The State University of New Jersey
October 1996 - December 2001

Publications

Publications (44)
Article
Full-text available
Non-coding RNA regulatory elements are important for viral replication, making them promising targets for therapeutic intervention. However, regulatory RNA is challenging to detect and characterise using classical structure-function assays. Here, we present in cell Mutational Interference Mapping Experiment (in cell MIME) as a way to define RNA reg...
Article
Full-text available
The appearance of molecular replicators (molecules that can be copied) was probably a critical step in the origin of life. However, parasitic replicators would take over and would have prevented life from taking off unless the replicators were compartmentalized in reproducing protocells. Paradoxically, control of protocell reproduction would seem t...
Article
Full-text available
Among Candida species, the opportunistic fungal pathogen Candida glabrata has become the second most common causative agent of candidiasis in the world and a major public health concern. Yet, few molecular tools and resources are available to explore the biology of C. glabrata and to better understand its virulence during infection. In this study,...
Article
Full-text available
Riboswitches are non-coding elements upstream or downstream of mRNAs that, upon binding of a specific ligand, regulate transcription and/or translation initiation in bacteria, or alternative splicing in plants and fungi. We have studied thiamine pyrophosphate (TPP) riboswitches regulating translation of thiM operon and transcription and translation...
Article
Full-text available
The canonical activity of glycyl-tRNA synthetase (GARS) is to charge glycine onto its cognate tRNAs. However, outside translation, GARS also participates in many other functions. A single gene encodes both the cytosolic and mitochondrial forms of GARS but two mRNA isoforms were identified. Using immunolocalization assays, in vitro translation assay...
Article
RNA regulates many biological processes; however, identifying functional RNA sequences and structures is complex and time-consuming. We introduce a method, mutational interference mapping experiment (MIME), to identify, at single-nucleotide resolution, the primary sequence and secondary structures of an RNA molecule that are crucial for its functio...
Article
Assemble2 is an interactive graphical environment allowing a biologist to easily realize top-down and bottom-up approaches targeting the study and the creation of large and intricate RNA architectures. It consists of several interconnected parts: (i) a Java graphical interface allowing to visualize and interactively modify RNA 2D structures, (ii) t...
Chapter
Full-text available
Single-particle cryo-electron microscopy has the immense advantage over crystallography in being able to image frozen-hydrated biological complexes in their “native” state, in solution. For years the ribosome has been the benchmark sample for particles without symmetry. It has witnessed steady improvement in resolution from the very first single-pa...
Article
Full-text available
During assembly of HIV-1 particles in infected cells, the viral Pr55(Gag) protein (or Gag precursor) must select the viral genomic RNA (gRNA) from a variety of cellular and viral spliced RNAs. However, there is no consensus on how Pr55(Gag) achieves this selection. Here, by using RNA binding and footprinting assays, we demonstrate that the primary...
Article
Full-text available
The structure and function of conserved motifs constituting the apex of Stem I in T-box mRNA leaders are investigated. We point out that this apex shares striking similarities with the L1 stalk (helices 76–78) of the ribosome. A sequence and structure analysis of both elements shows that, similarly to the head of the L1 stalk, the function of the a...
Article
Full-text available
Ribosomes, the protein factories of living cells, translate genetic information carried by messenger RNAs into proteins, and are thus involved in virtually all aspects of cellular development and maintenance. The few available structures of the eukaryotic ribosome(1-6) reveal that it is more complex than its prokaryotic counterpart(7,8), owing main...
Conference Paper
Full-text available
Eukaryotic 80S ribosomes of known structure are far more complex than their 70S bacterial counterparts. Those from Saccharomyces cerevisiae, Tetrahymena thermophila, and Triticum aestivum, for example, bear insertions of ribosomal RNA (rRNA) called expansion segments (ES) and additional ribosomal proteins. The ribosomes of the kinetoplastid Trypano...
Article
Full-text available
A general approach for modeling the architecture of large and structured RNA molecules is described. The method exploits the modularity and the hierarchical folding of RNA architecture that is viewed as the assembly of preformed double-stranded helices defined by Watson-Crick base pairs and RNA modules maintained by non-Watson-Crick base pairs. Des...
Article
Full-text available
Protein synthesis in all living organisms occurs on ribonucleoprotein particles, called ribosomes. Despite the universality of this process, eukaryotic ribosomes are significantly larger in size than their bacterial counterparts due in part to the presence of 80 r proteins rather than 54 in bacteria. Using cryoelectron microscopy reconstructions of...
Article
Full-text available
Protein biosynthesis, the translation of the genetic code into polypeptides, occurs on ribonucleoprotein particles called ribosomes. Although X-ray structures of bacterial ribosomes are available, high-resolution structures of eukaryotic 80S ribosomes are lacking. Using cryoelectron microscopy and single-particle reconstruction, we have determined...
Article
Full-text available
Assemble is an intuitive graphical interface to analyze, manipulate and build complex 3D RNA architectures. It provides several advanced and unique features within the framework of a semi-automated modeling process that can be performed by homology and ab initio with or without electron density maps. Those include the interactive editing of a secon...
Article
Full-text available
It has long been accepted that the structural constraints stemming from the 3D structure of ribosomal RNA (rRNA) lead to coevolution through compensating mutations between interacting sites. State-of-the-art methods for detecting coevolving sites, however, while reaching high levels of specificity and sensitivity for Watson-Crick (WC) pairs of the...
Article
Full-text available
Software for visualizing sequence alignments and trees are essential tools for life scientists. In this review, we describe the major features and capabilities of a selection of stand-alone and web-based applications useful when investigating the function and evolution of a gene family. These range from simple viewers, to systems that provide sophi...
Article
Full-text available
Structural biology is rapidly accumulating a wealth of detailed information about protein function, binding sites, RNA, large assemblies and molecular motions. These data are increasingly of interest to a broader community of life scientists, not just structural experts. Visualization is a primary means for accessing and using these data, yet visua...
Chapter
Ribonuclease P constitutes a unique paradigm for understanding RNA recognition, RNA catalysis as well as RNA–protein assembly. The modeling efforts, aiming at unraveling the architectural features of this ribozyme and the molecular basis conferring specificity in recognition of the pre-tRNA substrate and of the protein cofactor, are summarized in t...
Article
Full-text available
The trimeric Sec61/SecY complex is a protein-conducting channel (PCC) for secretory and membrane proteins. Although Sec complexes can form oligomers, it has been suggested that a single copy may serve as an active PCC. We determined subnanometer-resolution cryo–electron microscopy structures of eukaryotic ribosome-Sec61 complexes. In combination wi...
Article
Full-text available
Multiple sequence alignments are powerful tools for understanding the structures, functions, and evolutionary histories of linear biological macromolecules (DNA, RNA, and proteins), and for finding homologs in sequence databases. We address several ontological issues related to RNA sequence alignments that are informed by structure. Multiple sequen...
Article
Full-text available
The range of functions ascribed to RNA molecules has grown considerably during recent years. Consequently, the analysis and comparison of RNA sequences have become recurrent tasks in molecular biology. Because the biological function of an RNA is expressed more by its folded architecture than by its sequence, original computational tools adapted to...
Article
Full-text available
The aim of the RNA Ontology Consortium (ROC) is to create an integrated conceptual framework-an RNA Ontology (RO)-with a common, dynamic, controlled, and structured vocabulary to describe and characterize RNA sequences, secondary structures, three-dimensional structures, and dynamics pertaining to RNA function. The RO should produce tools for clear...
Article
Full-text available
Efficient RNA sequence manipulations (such as multiple alignments) need to be constrained by rules of RNA structure folding. The structural knowledge has increased dramatically in the last years with the accumulation of several large RNA structures similar to those of the bacterial ribosome subunits. However, no tool in the RNA community provides a...
Article
Full-text available
Three programs have been developed to aid in the classification and visualization of RNA structure. BPViewer provides a web interface for displaying three-dimensional (3D) coordinates of individual base pairs or base pair collections. A web server, RNAview, automatically identifies and classifies the types of base pairs that are formed in nucleic a...
Article
A cyclic molecule constituted by (i) a hexameric PNA moiety complementary to six among the nine residues of the dimerization initiation site loop of HIV-1 and (ii) a spacer tethering the N- to the C-extremities of the PNA, has been elaborated to inhibit the dimerization process of HIV-1 genome. This compound has been synthesized following a liquid-...
Article
Full-text available
Although their genomes cannot be aligned at the nucleotide level, the HIV-1/SIVcpz and the HIV-2/SIVsm viruses are closely related lentiviruses that contain homologous functional and structural RNA elements in their 5′-untranslated regions. In both groups, the domains containing the trans-activating region, the 5′-copy of the polyadenylation signal...
Article
Full-text available
Retroviruses encapsidate their genome as a dimer of homologous RNA molecules noncovalently linked close to their 5' ends. The dimerization initiation site (DIS) of human immunodeficiency virus type 1 (HIV-1) RNA is a hairpin structure that contains in the loop a 6-nt self-complementary sequence flanked by two 5' and one 3' purines. The self-complem...

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Projects (4)
Project
Assemble2 is an interactive graphical environment allowing a biologist to easily realize top-down and bottom-up approaches targeting the study and the creation of large and intricate RNA architectures. It consists of several interconnected parts: (i) a Java graphical interface allowing to visualize and interactively modify RNA 2D structures, (ii) the 3D viewer UCSF Chimera and (iii) a set of web services wrapping algorithms predicting 2D and 3D RNA structures. Assemble2 has been used efficiently for the 3D modeling of several macromolecular complexes. Notably, it has been an essential part of the bioinformatics pipelines leading to the publication of high-resolution cryoEM structures of ribosomes for several eukaryotic organisms, from yeast to human.