RNA as a Catalyst

1
RNA as a Catalyst
In looking at present-dayprotein synthesis, one
is struck by the considerable involvement of
non-informational nucleic acidRibosomes are
mainly made from RNA, and adapter molecules
(tRNA) are exclusively made RNA. Why is this? We
cannot help feeling that the more significant
reasonis that they were part of the primitive
machinery for protein synthesis. In fact, tRNA
looks like Natures attempt to make RNA do the
job of a proteinIt is not impossible to imagine
that the primitive machinery had no protein at
all and instead consisted entirely of RNA. If
indeed rRNA and tRNA were essential parts of the
primitive machinery, one naturally asks how much
protein, if any, was then needed. It is tempting
to wonder if the primitive ribosome would have
been made entirely of RNAWe are faced with the
origin of all of this RNAPossibly the first
enzyme was an RNA molecule with replicase
properties. Crick J. Mol. Biol. 38, 367 (1968)
2
Structure of 50S Ribosomal Subunit
RNA
protein
peptidyl transferase
Steitz Science 289, 920 (2000)
3
Secondary Structure of Major rRNA
5 Half
3 Half
4
(No Transcript)
5
A Proposed Mechanism of Peptide Synthesis
Catalyzed by the Ribosome
Steitz Science 289, 920 (2000) Fig. 9. A
proposed mechanism of peptide synthesis catalyzed
by the ribosome. A2486 (A2451) is shown as the
standard tautomer in all steps, but could be
represented as the imino tautomer, which would
have a negative unprotonated N3 and a neutral
protonated N3. We expect that the electronic
distribution is actually between these two
extremes. (A) The N3 of A2486 abstracts a proton
from the NH2 group as the latter attacks the
carbonyl carbon of the peptidyl-tRNA. (B) A
protonated N3 stabilizes the tetrahedral carbon
intermediate by hydrogen bonding to the oxyanion.
(C) The proton is transferred from the N3 to the
peptidyl tRNA 3' OH as the newly formed peptide
deacylates. Among the variations on this
mechanism that should be considered would be a
protonated A2486 stabilizing the intermediate, as
in (B), with less contribution on acid-base
catalysis, as shown in (A) and (C).