1. Le repliement de l’ARN I

2. Overview Some rules of RNA architecture
Catalytic RNA : links between architecture and catalysis
Riboswitches : architecture stabilization by small ligands
RNA-protein assemblies
RISC components
Functional ribosomal structures

3. Basic principle of molecular biology
The unidirectional flux of biological information
Transcription
Translation
DNA
Protein
RNA
Ribosomes and
Transfert RNAs

4. Basic principle of molecular biology
The unidirectional flux of biological information
Transcription
Translation
DNA
RNA X
Protein
Epigenetics

5. Regulator RNA
Non coding RNA - Functional RNA molecules which do not code for a protein
RNAi - RNA interfering gene expression (1998)
Micro RNA- RNA molecules which either degrade or interfere with the expression of a mRNA (2001)

6. Types of functional RNAs
RNAs where the function is controlled by Watson-Crick base pairs
RNAs where the function is controlled
by the RNA architecture and the
Non-Watson-Crick base pairs

7. 3D 2D
The RNA code

8. Some chemistry and structure of RNA

9. Life is chemistry
Molecules attract each other, repel each other, interact with each other, form and break bonds

10. Chemistry needs structure
Molecules need precise architectures and positions in space to function in an orderly fashion with specificity

11. Biological evolution works only with and through molecules
Biological function captures molecular architectures

12. DNA
RNA
Phosphodiester
Linkage

13. Nucleic acids are negatively charged biopolymers ...
ADENINE (A)
THYMINE (T)
GUANINE (G)
CYTOSINE (C)
5 ’ OH
(Uracil)
RNA
3 ’

14. RNA, Main parts 5’ 3’

15. The negative charge is delocalized on the phosphate group

16. The polynucleotide
backbone
has a
polarity

17. Charge
delocalization D+ D-
Tautomeric
forms

18. Protonation
possibilities

19. Always
seen
Never
seen

20. Modified bases
have different … …
electronic
properties

21. H-bond characteristics

22. Horizontal
Interactions
Base pairing.
In helices
Complementary
Watson-Crick

23. Vertical interactions : stacking

24. Stacking forces Driving Force : hydrophobic effect. Not very specific
Partition in
very polar regions (phosphates) &
less polar ones (exocyclic groups of bases)

25. Stereochemistry of RNA 5 ’ 3 ’ P O5 ’ C5 ’ C4 ’ C3 ’ O3 ’ Nucleotide i
5 ’ P
O5 ’
C5 ’
Nucleotide i
C4 ’
C3 ’
O3 ’
Nucleotide i+1
3 ’

26. Torsion angles preferences :
1.Helices & 2. Single strands
O3'-P
C3'-O3'
C4'-C3'
C5'-C4'
O5'-C5'
P-O5'
gauche-
gauche+
trans 1. 60
120
180
240
300
360 2.
C2 ’-endo
C3 ’-endo 1

28. A-form helices
B-form helices

29. Several asymmetries nucleotides & polynucleotides:
- sugars are chiral
- 5’ > 3’ polarity in linkages
- strands are antiparallel
- helices are right-handed
- sugars are disposed asymmetrically with
respect to the paired bases

30. petit
sillon
grand
Minor
groove
Major
groove 34

31. Watson-Crick pairs are
isosteric

36. Major/deep groove 5’ 3’
Minor/shallow groove

37. Major/deep groove 5’ 3’
Minor/shallow groove

38. Main building block :
the RNA double helix
held together by
Watson-Crick pairs

41. Code de reconnaissanceG C A T
grand sillon
petit sillon
= accepteur de liaison H
= donneur de liaison H
= atome d’hydrogène
= groupement méthyle
Code de reconnaissance

43. RNA base pairing Non-Watson-Crick base pairs Watson-Crick base pairs
Form double stranded helices
C3’-endo & preferred conformers
Define the 2D structure (Main building block)
Dependence on monovalent ions
Non-Watson-Crick base pairs
Form RNA modules
C3’-endo & C2’-endo with less preferred conformers
Responsible for RNA-RNA recognition & 3D fold
Dependence on Divalent ions (Mg2+)

44. Nucleotide
3E/ 2E 3E
Non-W-C
W-C Helix
M2+ M+
2D structure
RNA motifs
Architecture

45. H-bond characteristics

46. Each base has
several H-bonding
donor and
acceptor sites

47. Three Interacting Edges
Hoogsteen Edge
Purines
Watson-Crick
Edge
Sugar
Edge

48. Interacting Edges
Pyrimidines
“CH” Edge
Watson-Crick
Edge
Sugar
Edge

49. Each base has three edges various H-bonding sites
and each edge carries
various H-bonding sites

50. Glycosidic Bond Orientation
Cis (default)
Trans

51. How to Annotate ?
RNA 7, 499 (2001)

52. Edge-to-Edge Pairing Types} { }
Watson-Crick
Hoogsteen
Sugar-edge
Watson-Crick
Hoogsteen
Sugar-edge {
Cis
Trans =
12 Basic Types
RNA 7, 499 (2001)

54. Diversity & Similarity in Tetraloops
C = G
5’  ’ A G U C
U-turn
Syn G

55. T-loops 23S rRNA tRNA = G G G Y G U U A T D A U C C G = C G = C 5’ 3 ’
5’  ’ A U
1387 G G
= G 18 D 16 U U C 53 54 59 60 55
5’  ’ T
1mA
G = C Y 61 58 G 57 56 A C
G = C

56. S-Motif Base-pairing 3’ 5 ’ A G A U G A A 5’ 3 ’ Trans Hoog./Sug. A•G
Trans W.C./Hoog.
U•A 3’
 5 ’ A G G U A A G A U G A A A 5’
Cis Hoog./Sug.
U•G
3 ’ 
Trans Hoog./Hoog. A•A