ayout 1 - EMBL Grenoble

Developmental Biology UnitCell polarity and RNA localisationPrevious and current researchPolarity is a main feature of eukaryotic cells, underlying many basic cellular functions and developmentalprocesses. Cell polarisation involves the targeting of cytoskeletal structures, organelles,and molecules, including RNAs to specific subcellular locations. RNA localisation coupled with localisedtranslational control is now recognised as a powerful, conserved and highly prevalentmechanism controlling the functional polarisation of cells, yet the mechanisms regulating theseprocesses are still poorly understood.In Drosophila, asymmetrically localised cell fate determinants in the oocyte specify the body axesand patterning of the future embryo. The key determinants, bicoid, gurken and oskar, are localisedas mRNAs and locally translated, ensuring the spatial restriction of their activities. Proper cytoskeletalorganisation and specific motor proteins are required for mRNA targeting. Using theseRNAs as models, our research is concerned with understanding how RNA localisation and translationalcontrol are regulated in space and time.Of particular interest is oskar, which regulates abdomen formation and induces germline formationin the fly. Ectopic oskar activity causes severe developmental defects, hence its tight spatial restrictionis critical. This is achieved by RNA localisation-dependent translation: oskar translationis repressed during transport and activated when the mRNA reaches the posterior pole. Multiplemechanisms then cooperate to achieve tight anchoring of the mRNA andprotein at the posterior.Anne EphrussiPhD 1985, MassachusettsInstitute of Technology.Postdoctoral research atHarvard University andWhitehead Institute, MIT,Cambridge, Massachusetts.Group leader at EMBL since1992. Coordinator of EICATsince 2005; Unit Coordinatorsince 2007.The Drosophila oocyte is ideally suited for genetic, biochemical and cell biologicalinvestigation of the processes of cell polarisation, mRNA localisationand translational control. We make use of this model system tostudy (1) cytoskeletal polarisation, (2) the assembly of the RNA transportcomplexes and their association with motors and the cytoskeleton mediatingtheir movement, (3) spatial control of translation within cells.Future projects and goalsCombining genetics, proteomics, biochemistry, and a broad spectrum ofcell biological approaches, from electron microscopy to live cell imaging,we are investigating:• the mechanisms underlying cell polarisation;A Drosophila egg-chamber, showing co-localisation ofoskar mRNA, Staufen protein and a microtubule polaritymarker at the posterior of the oocyte.• the role of the cytoskeleton and motors in mRNA transport;• the architecture of transport RNPs: the cis-acting RNA elementsand interacting proteins, and how they assemble to form functional RNA transport complexes;• the mechanisms coupling mRNA localisation and translational control;• how Oskar protein nucleates formation of the polar granules, the germline granules of Drosophila.Our goal is to understand the basic mechanisms underlying RNA transport and spatial control of translation, and how they cooperate to generatea correctly patterned embryo.Selected referencesBesse, F., Lopez de Quinto, S., Marchand, V., Trucco, A. & Ephrussi,A. (2009). Drosophila PTB promotes formation of high-order RNPparticles and represses oskar translation. Genes Dev., 23, 195-207Besse, F. & Ephrussi, A. (2008). Translational control of localizedmRNAs: restricting protein synthesis in space and time. Nat. Rev.Mol. Cell Biol., 9, 971-80Vanzo, N., Oprins, A., Xanthakis, D., Ephrussi, A. & Rabouille, C.(2007). Stimulation of endocytosis and actin dynamics by Oskarpolarizes the Drosophila oocyte. Dev. Cell, 12, 53-555.Chekulaeva, M., Hentze, M.W. & Ephrussi, A. (2006). Bruno acts as adual repressor of oskar translation, promoting mRNA oligomerizationand formation of silencing particles. Cell, 12, 521–533.Hachet, O. & Ephrussi, A. (200). Splicing of oskar RNA in thenucleus is coupled to its cytoplasmic localization. Nature, 28, 959-96323