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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
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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
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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
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RNA absent from regulation networks
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KEGG regulation network for actin biosyntesis, modified by Clement & Zucker
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Target prediction
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Mixed results, lots of False Positives
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Taking accessibility into account
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Hofacker 2007
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sRNA tend to bind via accessible regions
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dsrA ryhB oxyS
Bind to targets
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Target prediction with accessibility
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Improved results, but far from perfect
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Obstacles to correct target prediction
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Chevalier et al. 2010
The Hfq chaperone
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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
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arcZ
sdaC
STM3216tpx
Accessibilité
Conservation
Résultante
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micC ompC
Accessibilité
Conservation
Résultante
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ryhBsdhC
Accessibilité
Conservation
Résultante
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oxySHfq binding sitefhlA fhlA
Accessibilité
Conservation
Résultante
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Constraints on sRNA vs. mRNA
Target 1
Target 2
Target 3
Target 4
sRNA
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sRNA vs. Target conservation
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0
20
40
60
80
100
120
140
160
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
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mRNA conservation
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-1
Average E. coli mRNAs
Average targetted mRNAs
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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
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Next developments
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sRNA mRNA1 mRNA2
Covariation
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Combine with phylogenetic profiling
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1070 bacterial genomes
Genes and RNA elements
Cluster of co-evolving RNAs and genes
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Acknowledgements
Alban OttAntonin Marchais
RNA sequence, structure & function lab
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