A hierarchical model for
evolution of ribosomal RNA
Konstantin Bokov and
Sergey Steinberg
Université de Montréal
1
The ribosome is a universal
machine producing proteins
LARGE
SUBUNIT
GROWING
PROTEIN
- addition of new peptides
to the growing protein chain
(in PTC);
PTC
P A
SMALL
SUBUNIT
5’
2
TRANSPORT
RNA
DR
- correct decoding of the
messenger RNA (in DR);
- precise movement along
the messenger RNA;
- coordination of the work of
all co-factors and ligands;
MESSENGER
RNA
The evolution of Life on Earth
directly depends on the
emergence of the ribosome !
Protein
World
3
The ribosome and LUCA
Bacteria
Archaea
Eukarya
Last
Universal
Common
Ancestor
4
Functionality of the ribosome
depends primarily on its RNA
Small
subunit
+
RNA
Large
subunit
+
proteins
RNA
RNA+proteins
proteins
Protein-WORLD
RNA-WORLD
5
RNA-body
Major periods in the evolution
of the ribosomal RNA
Unlimited
reshuffling
of RNA chains
F
PROTO
RIBOSOME
6
F
F
Restricted step-wise increase of
the ribosome size
MODERN
RIBOSOME
Preserve functional structure !
gene sequence
insertion
5’
7
3’
5’
3’
Accommodation of an insertion
gene sequence
insertion
Broken
8
Unstable
gene sequence
Stable
General principle of insertion:
Structural integrity of more
ancient elements cannot be
dependent on the presence of
more recently acquired
elements.
9
Integrity of each strand of a
double helix depends on the
presence of the other strand
10
5’
3’
3’
5’
The A-minor motif as an
evolutionary determinant
23S rRNA
A-minor
motif
11
Nissen, P., Ippolito, J.A., Ban. N., Moore, P.B., Steitz, T.A. (2001) RNA
tertiary interactions in the large ribosomal subunit: the A-minor motif.
Proc Natl Acad Sci U S A. No 98(9), pp. 4899-4903.
In a newly emerged element:
1. The 3’- and 5’-termini must be close to
each other
2. For each double helix, both strands must
be present
3. When such element forms an A-minor
interaction with the other elements of the
ribosome, it must provide the adenosine
stack and not the double helix
12
Dismantling the ribosomal RNA:
removal of those elements that
are qualified as the most recent
acquisitions of the ribosomal
structure
MODERN
RIBOSOME
PROTORIBOSOME
core
13
Last acquisitions
2-nd last acquisitions
Dismantling the structure
of the 23S rRNA
14
Inter-domain A-minor interactions
double helix
A-min
15
stack of adenosines
Dismantling the structure
of the 23S rRNA
16
The symmetrical structure in Domain
V is the proto-ribosome
P-site
A-site
t-RNA
17
The network of dependencies does
not contain cycles
18
59
54
If the orientations of all A-minor
interactions in the 23S rRNA were
chosen randomly, the probability of a
cycle-free arrangement would be P<
-9
10 .
The absence of cycles of dependency is a
fundamental characteristic of the 23S rRNA,
which is directly related to the particular
trajectory of its emergence.
19
Growing support for PTC
20
Appearance of the protuberances and
of the small subunit
22
What about 16S rRNA?
SSU
21
LSU
The hypothetical structure of the
primordial ribosome and two tRNAs
25
Small world...
26
Acknowledgment
We appreciate
the help of
NSERC and CIHR
for financing
this project.
presentation
Chain of A-minor interactions
E-coli, 23S
E-coli, 23S
A-stack (in red)
E-coli, 23S
A-stack (in red)
Non-covalent
dependency
A-stack (in red)
H69
H92
H71
H71
H68
H69
H95
H92
H93
H95
H74
H93
H74
H68
A
Double helix is
older than stack
of A-s packing in
its minor groove
Pseudoknot
B
A
C
The loop of a stem-loop structure (A) forms a
double-helix (B) with a region outside this
stem-loop
for example with another stem-loop (C)
B
Pseudoknots in the 23S rRNA
C
- local
- non-local
Long-distance pseudoknots in
the 23S rRNA
33
40
D
40
The approach is applicable
Along-groove packing” motif as
a mean of structural fitting
E-coli, 23S
H25 minor groove
G17-C523
G539-U554
H2
H25
(G-C)
(G-U)
H2 minor groove
F
Along-groove packing motif
Along-groove packing motif
G
AGPM-s in 23S rRNA
H
What about evolutionary
deletions ?
X
B
evolution
A
L
C
=A-D
Accommodation must not
provoke structure weakening
?
M
Additional
Notion of dependency
Covalent dependency
Non-covalent dependency (A-min)
E-coli, 23S
E-coli, 23S
E
Core
A
B
C
D
B
yellow
A-stacks
In PCK
WC helices
A
E
B
C
D
C
A
Core
The new RNA insertion covalently depends
on the structure where it emerged
N
B
A
C
A
A
The element containing stack of adenosines is noncovalently dependent on its complimentary WC helix
Domain-V is the most ancient part
of the ribosome
P
16S mitochondrial versus prokaryotes
Only prokaryotes
R
Mito and prokaryotes
23S mitochondrial versus prokaryotes
Only prokaryotes
S
Mito and prokaryotes
Dismantling versus evolution
PROTORIBOSOME
MODERN
RIBOSOME
T
MODERN
RIBOSOME
PROTORIBOSOME
AGPMs in the ribosome of E.coli
19
54
26
26
11
11
25
47
36
27
45
57
40
51
20
40
The evolution of Life on Earth
directly depends on the
emergence of the ribosome !
Protein
World
2