phylogenetic signatures of rna-rna contacts in bacteria 1 daniel gautheret institut de génétique...
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Phylogenetic signatures of RNA-RNA contacts in bacteria
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Daniel Gautheret
Institut de Génétique et MicrobiologieCNRS-Université Paris-Sud
RNA-based gene regulation
• In eukaryotes: RNAi, microRNA (1990’s)
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RNAi and miRNA function
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Dicer
ds RNA
Regulatory RNA
Ago
Target mRNA
Degradation orTranslation stop
Bacterial sRNA (1980’s)
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RNA: the ideal information-based regulator
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G
GG
GA
AA
C
CU
C
C UU
Regulatory sequences dictate targets
Universal
RNA absent from regulation networks
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KEGG regulation network for actin biosyntesis, modified by Clement & Zucker
Target prediction
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Mixed results, lots of False Positives
Taking accessibility into account
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Hofacker 2007
sRNA tend to bind via accessible regions
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dsrA ryhB oxyS
Bind to targets
Target prediction with accessibility
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Improved results, but far from perfect
Obstacles to correct target prediction
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Chevalier et al. 2010
The Hfq chaperone
Using sRNA conservation
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Sequence
Escherichia coli k12 MG1655 ACGAGUGCGGCACG
Escherichia coli O157H7 EDL933 AACGGAGCGGCACC
Shigella flexneri 2a -ACGAAGCTGCACC
Yersinia pestis Antiqua AACGAAG--GCACC
1 x 0,010 x 0,21 x 0,6
dsrA
reference
conservation
Weighted by evolutionary distance
Pairwise Blast vs. all complete genomes
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dsrArpoS
hns
Accessibilité
Conservation
Résultante
arcZ
sdaC
STM3216tpx
Accessibilité
Conservation
Résultante
micC ompC
Accessibilité
Conservation
Résultante
ryhBsdhC
Accessibilité
Conservation
Résultante
oxySHfq binding sitefhlA fhlA
Accessibilité
Conservation
Résultante
Constraints on sRNA vs. mRNA
Target 1
Target 2
Target 3
Target 4
sRNA
sRNA vs. Target conservation
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0
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40
60
80
100
120
140
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dsrAoxyS fhlA hns
rpoSompC
micCryhB sdhC
69
11
110
99
142
14 139
24# species with homology
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40
60
80
100
120
140
mRNA conservation
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-1
Average E. coli mRNAs
Average targetted mRNAs
Profile clustering: 5’ regions of mRNAs
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3/45 vs 35/2097 Pvalue : 0.049
2/63 vs 35/2097 Pvalue : 0.030
4/50 vs 35/2097 Pvalue : 0.014
Next developments
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sRNA mRNA1 mRNA2
Covariation
Combine with phylogenetic profiling
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1070 bacterial genomes
Genes and RNA elements
Cluster of co-evolving RNAs and genes
Acknowledgements
Alban OttAntonin Marchais
RNA sequence, structure & function lab
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