[
Environ Microbiol Rep,
2011]
Bacteria of the genus Legionella persist in a wide range of environmental habitats, including biofilms, protozoa and nematodes. Legionellaceae are 'accidental' human pathogens that upon inhalation cause a severe pneumonia termed 'Legionnaires' disease'. The interactions of L. pneumophila with eukaryotic hosts are governed by the Icm/Dot type IV secretion system (T4SS) and more than 150 'effector proteins', which subvert signal transduction pathways and promote the formation of the replication-permissive 'Legionella-containing vacuole'. The Icm/Dot T4SS is essential to infect free-living protozoa, such as the amoeba Dictyostelium discoideum, as well as the nematode Caenorhabditis elegans, or mammalian macrophages. To adapt to different niches, L. pneumophila not only responds to exogenous cues, but also to endogenous signals, such as the -hydroxyketone compound LAI-1 (Legionella autoinducer-1). The long-term adaptation of Legionella spp. is based on extensive horizontal DNA transfer. In fact, Legionella spp. have acquired canonical 'genomic islands' of prokaryotic origin, but also a number of eukaryotic genes. Since many aspects of Legionella virulence against environmental predators and immune phagocytes are similar, an understanding of Legionella ecology provides valuable insights into the pathogenesis of legionellaceae for humans.
[
Proc Natl Acad Sci U S A.,
2005]
MicroRNAs (miRNAs) are a recently discovered set of regulatory genes that constitute up to an estimated 1% of the total number of genes in animal genomes, including Caenorhabditis elegans, Drosophila, mouse, and humans [Lagos-Quintana, M., Rauhut, R., Lendeckel, W. M Tuschl, T. (2001) Science 294, 853-858; Lai, E. C., Tomancak, P., Williams, R. W. M Rubin, G.M. (2003) Genome Biol. 4, R42; Lau, N. C., Lim, L. P., Weinstein, E. G. M Bartel, D. P. (2001) Science 294, 858-862; Lee, R. C. M Ambros, V. (2001) Science 294, 862-8644; and Lee, R. C., Feinbaum, R. L. M Ambros, V. (1993) Cell 115, 787-798]. In animals, miRNAs regulate genes by attenuating protein translation through imperfect base pair binding to 3' UTR sequences of target genes. A major challenge in understanding the regulatory role of miRNAs is to accurately predict regulated targets. We have developed an algorithm for predicting targets that does not rely on evolutionary conservation. As one of the features of this algorithm, we incorporate the folded structure of mRNA. By using Drosophila miRNAs as a test case, we have validated our predictions in 10 of 15 genes tested. One of these validated genes is mad as a target for bantam. Furthermore, our computational and experimental data suggest that miRNAs have fewer targets than previously reported.