Satellite Workshop Satellite Workshop on on RNA OntologyRNA Ontology

RNA 2005RNA 2005Tenth Annual Tenth Annual MeetingMeetingof the of the RNA SocietyRNA Society

Banff, May 23st and May Banff, May 23st and May 24rth24rth

Is there a danger, in Is there a danger, in molecular biology, that molecular biology, that the accumulation of the accumulation of data will get so far data will get so far ahead of its ahead of its assimilation into a assimilation into a conceptual framework conceptual framework that the data will that the data will eventually prove an eventually prove an encumbrance ?encumbrance ?

John MADDOX, 1988.John MADDOX, 1988.

All science is either All science is either physics or stamp physics or stamp collecting.collecting.

Rutherford.

The bacterial ribosome :The bacterial ribosome :

270 000 atoms (C,N, O, P)270 000 atoms (C,N, O, P)55 proteins55 proteins3 RNA (4600 nucleotides)3 RNA (4600 nucleotides)

Even with the knowledge of the quantum physics of Even with the knowledge of the quantum physics of water molecules, it would be impossible to deduce water molecules, it would be impossible to deduce the laws of formation of waves in the sea. Ken WILSON.the laws of formation of waves in the sea. Ken WILSON.

How can we go How can we go beyond organizing beyond organizing

data banks of data banks of Sequences,Sequences,Structures, Structures,

Motifs, Motifs, Genomes ?Genomes ?

Are our concepts relevant ?Are our concepts relevant ?

Towards a RNA ontology ?

Why do we bother about classification ?

What are our aims ?

2) Extract information about 3D folding;

1) Derive accurate & meaningfulalignments;

3) Derive rules for RNA evolution;

4) Search genomes for non-coding RNAs.

HW-C

HW-C

SUG

WATSON-CRICKH

W-C

SUG

HW-C

SUG

H

W-C

SUG

H

W-C

SUG

H

W-CS

UG

H

W-C

SUG

H

W-C

SUG

HW-C

SUG

HW-C

SUG

HW-C

SUG

CIS BASEPAIRS

TRANS BASEPAIRS

WATSON-CRICK

WATSON-CRICK

HOOGSTEEN

WATSON-CRICK

SUGAR-EDGE

HOOGSTEEN

HOOGSTEEN

HOOGSTEEN

SUGAR-EDGE

HW-C

HW-C

SUGH

W-C

SUG

W-C

H SUG

H

W-C

SUG

HW-C SU

G

H

W-CSUG

H

W-C

SUG

H

W-C

SUG

H

W-C

SUG

HW-C

SUG

HW-C

SUGWATSON-CRICK

WATSON-CRICK

WATSON-CRICK

HOOGSTEEN

WATSON-CRICK

SUGAR-EDGE

HOOGSTEEN

HOOGSTEEN

SUGAR-EDGE

SUGAR-EDGE

SUGAR-EDGE

SUGAR-EDGE

HOOGSTEEN

SUGAR-EDGE

Antiparallel Parallel Antiparallel Parallel Antiparallel

Parallel Antiparallel Parallel Parallel Antiparallel Parallel

Antiparallel

Physical entity : base or base pairAttributes: three edges

(W_C, H, S_E)Attribute: glycosidic angle

(syn or anti)

Non-physical entity : base pair relationshipAttribute: interacting edges

(ordered pair of edges)Attribute: orientations of glycosidic bonds

(cis or trans)

Many other molecular attributes…

Where to stop ?

Granularity within the Consortium

1. Tools for crystallographers- NDB tools- Jane Richardson (backbone)- Base pair families

2. Tools for the analysis, classification,and search of crystal structures - Backbone (Eli, Jane, …), SCOR

- Annotate (Major), RNAview (NDB) - s2s (Jossinet), FR3D (Leontis)

Granularity within the Consortium

3.Tools for alignments- RFAM- s2s

4. Tools for 1D to 2D- Mfold, …- D. Mathews

5. Tools for 1D/2D to 3D- McSYM- Manip/Fragment

(((( ((( ))) )))-)GCUG UUAGG GGA GUUUUA UCC AGCGU CAG-CGCCG UUAGG GGA GUUUCA UCC AGCGA UGG-CGUUG UAGG GGA GUCUCA UCC AGCA CAA-CGCUG GAGG GAA GC AA UUC AGCA CAG-CACUU CAGU GGA GC AA UCC AGCA GAGAUACUU CAGU GGA GC AA UCC AGCA GAGAUGAUG GAGG UUG G AAA CAA UGCA CAU-CGGGC CAGG GGU G AAA ACC AGCA GCC-AGGCC UAGG UCG G AAA CGG AGCA GGU-CGGCC CAGG UCG G AAA CGG AGCA GGU-CGGCC CAGG UCG G AAA CGG AGCA GGU-CGGCC CAGG UCG G AAA CGG AGCA GGU-CGGCC CAGG UCG G AAA CGG AGCA GGU-C

Comparisons of 3D structures

Comparisons of sequences

The K-turn The C-motif

K-Turn

Sugar-edge

Hoogst

een

A C G U

U

A

C

G

I1

I2

I1

I2

I1 I1

I1I1 I1

I2

transA C G U

U

A

C

G

I1

I1

I1

I1

(I2)

I2

I2

I2

trans

Sugar-edge

Sug

ar-

edge

I6

A C G U

U

A

C

G

i2

I3

I4

i2

I1

I1

I1

I1

I5

I2

cis

I3

I2

I5 I6Wats

on

-Cri

ckWatson-Crick

9282

10077

The K-turn motifThe K-turn motif

Watson-Crick

I6

A C G U

U

A

C

G

i2

I3

I4

i2

I1

I1

I1

I1

I5

I2

cis

I3

I2

I5 I6Wats

on

-Cri

ck

Cis Watson-Crick/Watson-crick

G85

C97

A C G U

U

A

C

G

7(0)

trans

0(7)

-

-

0(6)

801(786)

0(7)

0(3)

6(0)

11(17)0(3)

3(0)

9282

10077

Sugar-edge

Hoogst

eenA C G U

U

A

C

G

I1

I2

I1

I2

I1 I1

I1I1 I1

I2

trans

G97

A80

A C G U

U

A

C

G

675(673)

4(4)

145(145)

trans -

-

0(2)

A98

A C G U

U

A

C

G

583(580)

126(125)

113(112)

trans

0(1)

-0(3)

1(1)

0(1)

1(0)

0(3)

0(1)

3(0)

G79

-

Trans Hoogsteen/Sugar-edge

9282

10077

2(0)

0(2)

A C G U

U

A

C

G

I1

I1

I1

I1

(I2)

I2

I2

I2

trans

Sugar-edge

Sug

ar-

edge

A98

G81

A C G U

U

A

C

G

6(6)

trans -

-

810(807)

1(1)

1(4)

7(7)0(3)

3(0)

640(641)

3(2)

A80

G94

A C G U

U

A

C

G

38(38)

trans -

-

15(15)130(130)1(1)

Cis Sugar-edge/Sugar-edge

9282

10077

375

390

372

Hoogsteen

Wats

on

-Cri

ck

A C G U

U

A

C

G

I1

I4

I5

I4

I1I2 I2

I3

transA C G U

U

A

C

G

I1 I1 I1 I1

(I2) I2I2 I2

trans

Sugar-edge

Wats

on

-Cr i

c k

I6

A C G U

U

A

C

G

i2

I3

I4

i2

I1

I1

I1

I1

I5

I2

cis

I3

I2

I5 I6Wats

on

-Cri

ckWatson-Crick

The C motifThe C motif

(I3) I3 I3I5

I4 (I4) I4 (I4)

I4

I2

I6

A C G U

U

A

C

G

i2

I3

I4

i2

I1

I1

I1

I1

I5

I2

cis

I3

I2

I5 I6Wats

on

-Cri

ckWatson-Crick

The C The C motifmotif

0(1)

A C G

U

A

C

G 0(2)

0(16)

328(134)

2(0)

445(246)

0(182)

cis

0(12)

0(181)

0(1)

0(16)

U29(1)0(12)

-

-

1(1)

G371

C39

0

A C G

U

A

C

G

cis

0(1)

U804(801)

-

-

1(0)

U375

A3

89

0(1)

0(2)

0(2)

0(2)

The C The C motifmotif

A C G

U

A

C

G

29(29)

328(327)

2(0)

cis

3(3)

0(1)

U444(444)1(1)

-

-

C390

A3

74

A C G U

U

A

C

G

I1 I1 I1 I1

(I2) I2I2 I2

trans

Sugar-edgeW

ats

on

-Cr i

c k

(I3) I3 I3I5

I4 (I4) I4 (I4)0(1)

0(2)

The C The C motifmotif

A C G

U

A

C

G

804(803)

1(0)

cis

0(1)

U

1(1)

-

-

A389

C3

72 0

(1)

Hoogsteen

Wats

on

-Cri

ckA C G U

U

A

C

G

I1

I4

I5

I4

I1I2 I2

I3

trans

I4

I2

UG

CCUUGC

CC G

G

CACGCAAGG

GAU

GGUGUCA

AAU

U

GGCG

AAACGCCGA

GCC

AAG

C G

AA

G

U

GU

AGACG

GCACC

CA

CC

UAU

GUG

AAG

GC

A

U

100-

-120

90-

P1P3

P4

P6P8

J4/5

J8/7

15-

-55

-150

UGC

cadt

cda

g

20- -30

40-

95-

45-10-

-35

A A

-145

-141

-135

-125

47-48

47-48

-50

165-

-167

-169

+1

J3/4

J6/7

P2J2/3

C46

A97

G139

A98

J8/8a

-1

-3C

G

N6 O2'

N6 N1

N4 O2'

N7 N1

G

A

G N1O2'

UG

CCUUGC

CC G

G

CACGCAAGG

GAU

GGUGUCA

AAU

U

GGCG

AAC

AACGCCGA

GCC

AAG

C G

AA

G

U

GU

CUAGACG

GCACC

CA

CC

UAU

GUG

AAG

GC

A

UAG

100-

-120

90-

P1P3

P4

P5

P6P8

J4/5

J8/7

15-

CGG

-60

85-

-55

-150

UGCCG

cadt

cda

ggc5-

20- -30

40-

95-

45-10-

-35

A A

-145

-141

-135

-125

47-48

47-48

-50

165-

-167

-169

174-

+1

+5 P7P10

J3/4

J6/7

P2J2/3

C46

A97

G139

A98

J8/8a

-1

-3

C

C

G

N6 N1

B

N4 O2'

G

A

G