Phylogenetic signatures of rna rna contacts in bacteria
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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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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

RNA-based gene regulation

  • In eukaryotes: RNAi, microRNA (1990’s)


Rnai and mirna function

RNAi and miRNA function

ds RNA

Dicer

Ago

Regulatory RNA

Target mRNA

Degradation or

Translation stop


Bacterial srna 1980 s

Bacterial sRNA (1980’s)


Rna the ideal information based regulator

RNA: the ideal information-based regulator

Universal

G

C

C

A

G

U

U

G

A

U

C

C

A

G

Regulatorysequencesdictatetargets


Rna absent from regulation networks

RNA absent from regulation networks

KEGG regulation network for actin biosyntesis, modified by Clement & Zucker


Target prediction

Target prediction

Mixed results, lots of False Positives


Taking accessibility into account

Taking accessibility into account

Hofacker 2007


Srna tend to bind via accessible regions

sRNA tend to bind via accessible regions

ryhB

oxyS

dsrA

Bind to targets


Target prediction with accessibility

Target prediction with accessibility

Improvedresults, but far fromperfect


Obstacles to correct target prediction

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Obstacles to correct target prediction

The Hfqchaperone

Chevalier et al. 2010


Using srna conservation

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


Phylogenetic signatures of rna rna contacts in bacteria

dsrA

rpoS

Accessibilité

hns

Conservation

Résultante


Phylogenetic signatures of rna rna contacts in bacteria

arcZ

Accessibilité

STM3216

tpx

Conservation

sdaC

Résultante


Phylogenetic signatures of rna rna contacts in bacteria

micC

ompC

Accessibilité

Conservation

Résultante


Phylogenetic signatures of rna rna contacts in bacteria

ryhB

sdhC

Accessibilité

Conservation

Résultante


Phylogenetic signatures of rna rna contacts in bacteria

oxyS

fhlA

Hfq binding site

fhlA

Accessibilité

Conservation

Résultante


Constraints on srna vs mrna

Constraints on sRNA vs. mRNA

sRNA

Target 1

Target 2

Target 3

Target 4


Srna vs target conservation

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


Mrna conservation

mRNA conservation

AveragetargettedmRNAs

Average E. coli mRNAs

-1


Profile clustering 5 regions of mrnas

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


Next developments

Next developments

sRNA

mRNA1

mRNA2

Covariation


Combine with phylogenetic profiling

Combine with phylogenetic profiling

1070 bacterialgenomes

Genes and RNA elements

Cluster of co-evolvingRNAs and genes


Acknowledgements

Acknowledgements

Alban Ott

Antonin Marchais

RNA sequence, structure & function lab


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