Re: Why do self-sufficent 'ribozymes' use RNA and not DNA?

Blake,

You have asked some challenging questions, not all of which have definite 
answers.  Maybe I can help clear some things up. First of all, ribozymes 
are by definition composed of RNA; a deoxyribozyme (if it existed) would be 
composed of DNA.

The small differences between the properties of ribose versus deoxyribose 
sugars definitely favor RNA over DNA, anyway.  (I'm assuming you know a 
little about RNA and DNA to be asking such specific questions; if you need 
further clarification, let me know).  The structure of doubles stranded DNA 
is more narrow than RNA; there are differences in the depth of the major 
and minor grooves, the tilt of bases, the sugar pucker geometry, and most 
importantly, the thermodynamic stability of helical runs.  You know the two 
strands are held together by hydrogen-bonds, but the stacking energy 
between base pairs is what's relavent here.  The stacking energy for RNA 
base pairs is more stable than for DNA.  What is observed in nature are 
long runs (several kbases to Mbases) of helical DNA, while RNA duplex 
regions tend to be short (between 5 and 15 base pairs, generally).  RNA's 
tend to be interspersed with loops, bulges, etc., while these non-base 
paired regions are generally absent in DNA.  There are functional reasons 
for this as well; proteins can't access the major groove of RNA (too deep) 
like DNA binding proteins do.  So, RNA binding proteins interact with these 
"non-structured" regions.  There's more I can tell you if you're 
interested, but let's get to your real question.

Why do we think RNA was the pre-biotic molecule?  First, we need to define 
the criteria for such a molecule.

1) All of the functions in the cell must be encoded by a single type of 
molecule; the expectation is that the pre-biotic molecule should be a 
polymer (this is cheating, since we know DNA, RNA, and proteins are all 
polymers, but it's part of the argument anyway).

2) The individual polymer units must be formed by natural organic 
chemistry.  Actually, several groups have shown that both nucleotides and 
amino acids can be formed under conditions thought to mimic primordial 
life.  Everything we would need can be created from individual elements and 
energy (either heat or electricity), given enough time.  These are 
incredibly slow, inefficient reactions, but get us to where we need to
be.

3) The prebiotic molecule must be able to encode information

4) The prebiotic molecule must be able to catalyze it's own
replication

5) The prebiotic molecule must be able to catalyze other reactions (like 
protein synthesis, as we expect).


There are other things you can come up with too, but this is sufficient for 
an entry level discussion.

RNA meets these last three criteria, while DNA and proteins can not.  DNA 
has never been shown to have any catalytic function.  There are groups who 
can replace portions of catalytic RNA with DNA without losing function, but 
no one has made an all-DNA molecule with catalytic activity.  Proteins are 
certainly catalytic, but do not meet the information storage criteria, nor 
the self-replication one.  Proteins are made in the ribosome and are 
actually catalyzed by the RNA component of the ribosome, not the ribosomal 
proteins.  Tom Cech showed in 1982 that a bacterial RNA was capable of 
performing a self-cleavage reaction (he won the Nobel prize for it); since 
then, the ribosome field has been extremely active.  The original 
Tetrahymena Group I intron ribozyme that Dr. Cech discovered has been 
mutated by many other groups to perform splicing reactions, ligation 
reactions, replication reactions, and even peptidyl-trasnferase reactions. 
 (In English, it can break apart RNA or DNA, put them back together, make a 
short copy of itself, and put amino acids together).  RNA is considered to 
be the prebiotic molecule by default, since no one has discovered these 
functions in any other molecules.  It doesn't prove RNA was the origin of 
life, but there are few other candidates.

That's the RNA-centric theory in a nut-shell.

If you want more reading (fairly technical at times), you should check this 
book out; it's already lagging behind the current research field, but is 
recent enough to encompass most of the discussions you'll be interested in:

Title: The RNA world : the nature of modern RNA suggests a prebiotic RNA 
world
edited by Raymond F. Gesteland, John F. Atkins.

Publisher: Cold Spring Harbor, NY : Cold Spring Harbor Laboratory Press, 
1993.

Call Number: QP623 .R6 1993

Thanks for your question,

Dr. Jim Kranz

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Admin note:

Dan Lafontaine adds the following:

The view that "DNA has never been shown to have any catalytic function" is
an interesting view that has been believed for a long time until recently.
However, there is some evidence that DNA may indeed have catalytic
function.  See "A DNA enzyme that cleaves RNA", published in Chem
Biol. 1994 Dec;1(4):223-9.