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Phylogenetic signatures of RNA-RNA contacts in bacteria

Phylogenetic signatures of RNA-RNA contacts in bacteria. Daniel Gautheret Institut de Génétique et Microbiologie CNRS-Université Paris-Sud. RNA-based gene regulation. In eukaryotes: RNAi, microRNA (1990’s). RNAi and miRNA function. ds RNA. Dicer. Ago. Regulatory RNA. Target mRNA.

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Phylogenetic signatures of RNA-RNA contacts in bacteria

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  1. Phylogenetic signatures of RNA-RNA contacts in bacteria Daniel Gautheret Institut de Génétique et Microbiologie CNRS-Université Paris-Sud

  2. RNA-based gene regulation • In eukaryotes: RNAi, microRNA (1990’s)

  3. RNAi and miRNA function ds RNA Dicer Ago Regulatory RNA Target mRNA Degradation or Translation stop

  4. Bacterial sRNA (1980’s)

  5. RNA: the ideal information-based regulator Universal G C C A G U U G A U C C A G Regulatorysequencesdictatetargets

  6. RNA absent from regulation networks KEGG regulation network for actin biosyntesis, modified by Clement & Zucker

  7. Target prediction Mixed results, lots of False Positives

  8. Taking accessibility into account Hofacker 2007

  9. sRNA tend to bind via accessible regions ryhB oxyS dsrA Bind to targets

  10. Target prediction with accessibility Improvedresults, but far fromperfect

  11. Javascript is required to show this page properly. • Drag image to reposition. Double click to magnify further. • Javascript is required to show this page properly. • Drag image to reposition. Double click to magnify further. Obstacles to correct target prediction The Hfqchaperone Chevalier et al. 2010

  12. Using sRNA conservation Pairwise Blast vs. all completegenomes Escherichia coli k12 MG1655 ACGAGUGCGGCACG Escherichia coli O157H7 EDL933 AACGGAGCGGCACC Shigella flexneri 2a -ACGAAGCTGCACC Yersinia pestis Antiqua AACGAAG--GCACC reference 1 x 0,01 0 x 0,2 1 x 0,6 Weighted by evolutionary distance conservation dsrA Sequence

  13. dsrA rpoS Accessibilité hns Conservation Résultante

  14. arcZ Accessibilité STM3216 tpx Conservation sdaC Résultante

  15. micC ompC Accessibilité Conservation Résultante

  16. ryhB sdhC Accessibilité Conservation Résultante

  17. oxyS fhlA Hfq binding site fhlA Accessibilité Conservation Résultante

  18. Constraints on sRNA vs. mRNA sRNA Target 1 Target 2 Target 3 Target 4

  19. sRNA vs. Target conservation 142 140 120 110 100 99 # species with homology 80 69 60 40 24 20 14 13 11 9 ryhB oxyS dsrA ompC hns rpoS fhlA sdhC micC

  20. mRNA conservation AveragetargettedmRNAs Average E. coli mRNAs -1

  21. Profile clustering: 5’ regions of mRNAs 4/50 vs 35/2097 Pvalue : 0.014 3/45 vs 35/2097 Pvalue : 0.049 2/63 vs 35/2097 Pvalue : 0.030

  22. Next developments sRNA mRNA1 mRNA2 Covariation

  23. Combine with phylogenetic profiling 1070 bacterialgenomes Genes and RNA elements Cluster of co-evolvingRNAs and genes

  24. Acknowledgements Alban Ott Antonin Marchais RNA sequence, structure & function lab

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