Units

Molecular biology of the gene

Person in charge of the Unit : Oui

Regulation of gene expression is fundamental for cell homeostasis and invariably leads to severe human pathogenesis when defective. Therefore, novel treatment strategies for a number of different diseases may depend on our ability to exploit mechanisms that normally alter the expression of endogenous genes. While historically, gene regulation studies have mostly focused on transcription, it has recently become evident that post-transcriptional levels of control play an equally important role. From the very onset of transcription, mRNAs have a complex existence: they are bound by the abundant shuttling hnRNPs proteins, processed at their 5'- and 3' ends (capping, poly-adenylation), internally processed and modified (splicing, editing,...), subjected to various nuclear quality controls (tested for the absence of premature stops,...), routed to the nuclear pore complex, translocated to the cytoplasm, translated (and/or stored) and eventually degraded. All these events are intimately fine-tuned and co-ordinated to ensure that Only 'proper' mRNAs are translated at the correct time and place. Our laboratory studies different aspects of postranscriptional gene regulation with a particular focus on the translation and stability control of mRNA containing so called AU-rich elements.

Projetcs

Study of the Post-transcriptional regulation mechanism mediated by the AU-rich sequences.

The AAu-rich sequences present in the 3' non transslated region of the mRNA of several cytokines, protooncogenes and growth factors are playing a crucial role in the stability and translation of the mRNA. The mechanisms of these reualtions are analysed.

Characterization of the AU-rich dependent mecanism of messenger RNAs degradation in Drosophila melanogaster.

Secretion of antimicrobial peptides (AMP) is a central defense mechanism used by invertebrates to combat infections. In Drosophila, the synthesis of these peptides is a highly regulated process allowing their rapid release in the hemolymph upon contact with pathogens and the arrest of their production after pathogen clearance. We observed that AMP genes have either a transient or sustained expression profile in S2 drosophila cells treated with peptidoglycan. Moreover, AMP genes containing AU-rich elements (ARE) in their 3' untranslated region (UTR) are subject to a post-transcriptional control affecting mRNA stability, thereby contributing to their transient expression profile. Cecropin A1 (CecA1) constitutes the prototype of this latter class of AMPs.

Characterization of TIAR and TIA-1 nucleo-cytoplasmic trafficking

Characterization of TIAR and TIA-1 nucleo-cytoplasmic trafficking