MadSci Network: Biochemistry

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

Date: Fri Nov 20 08:58:43 1998
Posted By: Dr. James Kranz, Post-doc, Biochem & Biophys
Area of science: Biochemistry
ID: 910839100.Bc


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

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.

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