|Drosophila genetics and epigenetics - CNRS URA 2578|
|HEAD||Dr Christophe ANTONIEWSKI / firstname.lastname@example.org|
|MEMBERS||Bassam Berry / Dr Corinne Besnard-Guerrin / Dr Anne-Laure Bougé / Dr Delphine Fagegaltier / Caroline Jacquier / Josette Pidoux /Dr Hélène Thomassin
Three classes of non-coding small RNAs mediate gene silencing in 21-nt siRNAs are produced from long double-stranded RNAs by Dicer-2 and trigger RNAi. The RNAi pathway provides the main defense against RNA viruses in plant and insects. ~23-nt miRNAs are processed from genome-encoded stem-loop precursors by Dicer-1 and repress mRNAs. Over the past few years, miRNAs have emerged as important regulators of development, cell proliferation and cell homeostasis. ~25-nt piRNAs derive from pericentromeric transposons transcripts through a “Ping-Pong” mechanism mediated by the Piwi, Aubergin and Argonaute-3 Argonautes. The piRNA pathway silences transposons in the germ line and has been involved in heterochromatin formation.
Deciphering the role of small RNAs in the regulation of Drosophila genome.
Our projects are aimed at understanding the role of small RNAs in the regulation of gene expression and chromosome structure in Drosophila.
We established a reporter system based on GFP silencing by artificial miRNAs. Using this reporter system, we performed wide-genome RNAi screen in cultured cells and identified genes potentially involved in the biogenesis and/or the activity of miRNAs. We are currently characterizing these candidates.
We have built, in collaboration with Pasteur-Génopole®, LNA oligonucleotide microarrays to perform genome wide analyses of miRNA expression profiles during development. Using this approach, we identified miRNAs induced at the onset of metamorphosis and potentially involved in the hormonally regulated genetic cascade that orchestrates Drosophila development during this period. We are also involved in collaborations to characterize miRNAs involved in immune responses to pathogens, aging and neurodegenerative diseases.
Another experimental approach consists in perturbing small RNA pathways by expressing proteins that sequester siRNAs and block their silencing activity. We have tested a battery of such inhibitors naturally encoded by a variety of plant viruses to counteract antiviral RNAi host responses and shown that they also function as potent RNAi inhibitors in Drosophila. Indeed, these RNAi suppressors dramatically increase susceptibility to viral infections, demonstrating that RNAi is a genuine antiviral response in this organism. We have recently shown that RNAi suppressors perturb in addition heterochromatin structure in somatic tissues, by sequestering endogenous siRNAs derived from transposons transcripts. This demonstrate that with regard to the control of chromatin dynamics, siRNAs play in somatic tissues a role similar to the one of piRNAs in the germ line.
Keywords: RNAi – Chromatin structure - Epigenetics – miRNA – siRNA - Drosophila – metamorphosis – Ecdysone – antiviral immune response.
Carre, C., Szymczak, D., Pidoux, J., and Antoniewski, C. (2005). The Histone H3 Acetylase dGcn5 Is a Key Player in Drosophila melanogaster Metamorphosis. Mol Cell Biol 25, 8228-8238.
Colombani, J., Bianchini, L., Layalle, S., Pondeville, E., Dauphin-Villemant, C., Antoniewski, C., Carre, C., Noselli, S., and Leopold, P. (2005). Antagonistic actions of ecdysone and insulins determine final size in Drosophila. Science 310, 667-670.
van Rij, R.P., Saleh, M.C., Berry, B., Foo, C., Houk, A., Antoniewski, C., and Andino, R. (2006). The RNA silencing endonuclease Argonaute 2 mediates specific antiviral immunity in Drosophila melanogaster. Genes Dev 20, 2985-2995.
Jaubert, S., Mereau, A., Antoniewski, C., and Tagu, D. (2007). MicroRNAs in Drosophila: the magic wand to enter the Chamber of Secrets? Biochimie 89, 1211-1220.
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Activity Reports 2007 - Institut Pasteur
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