Drosophila genetics and epigenetics - CNRS URA2578  

  HEADDr ANTONIEWSKI Christophe / antoniew@pasteur.fr

  Annual Report

Small RNAs

Several classes of 20-30 nt non-coding RNAs mediate gene silencing in eukaryotes. Small interfering RNAs (siRNAs) and repeat-associated siRNAs (rasiRNAs) most often derive from the cleavage of long dsRNA precursors by the RNase Dicer. They trigger degradation of complementary mRNAs and have been implicated in defense against viruses and transposable elements, chromosome heterochromatinization and chromosome imprinting. MicroRNAs (miRNAs) are expressed as stem-loop precursors and maturated by Drosha and Dicer RNases. MiRNA and siRNA pathways are overlapping. However, instead of functioning as guide for mRNA degradation, miRNAs inhibit the translation of their targets. Over the past few years, miRNAs have emerged as new regulators of essential processes such as development, cell proliferation and cell homeostasis.

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 have built, in collaboration with Pasteur-Génopole®, LNA oligonucleotide microarrays to perform genome wide analyses of miRNA expression profiles. We will particularly investigate and identify 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 interested in characterizing miRNAs involved in immune responses to pathogens, aging and sexual differentiation. Another experimental approach consists in perturbing small RNA pathways by expressing proteins that sequester small RNAs 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 Drosophila susceptibility to viral infections, demonstrating that RNAi is a genuine antiviral response in this organism. We have also shown that RNAi suppressors perturb heterochromatin structure by sequestering rasiRNA. Using RNAi suppressors as bait in immunoprecipitation experiments, we are currently cloning and sequencing these small RNA species. Last, we have set up a reporter system based on GFP silencing by artificial miRNAs. Using this system, we initiated two wide-genome screening strategies in cultured cells and flies to isolate and characterize genes involved in the biogenesis and/or the activity of miRNAs.


The white gene is silenced by RNAi (left) which is in turn suppressed by expression of the B2 protein from the FHV, restoring wild-type eye color (right).


Publications 2006 of the unit on Pasteur's references database

Activity Reports 2006 - Institut Pasteur
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