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RNA as a Catalyst
Name: Neeraja
Status: other
Grade: other
Location: Outside U.S.
Country: USA
Date: Winter 2011-2012
Question:
Why is RNA a better catalyst than DNA? Specifically what features of its structure make it better and why?
Replies:
Neeraja,
It's a good question, and my short answer is that it's because nucleic
acid enzymes must be single-stranded (ss), and there's a lot more
ss-RNA around than ss-DNA. Also, ss-RNA is more flexible than ss-DNA.
Adding the two together, you get two strong reasons why RNA is a
better chemical for this purpose than DNA. For a little more detail,
keep reading:
First, let me start with a basic explanation of how catalysis works: A
biological catalyst, whether protein or nucleic acid, is a
three-dimensional molecule with a specific 3D shape and chemical
surface properties. The way biological catalysts work is by having one
or more areas on their surface where target molecule(s) can attach.
The molecules attach because the catalyst surface has the right kind
of chemistry and shape for them to "fit" (by "fit", I mean the system
has lower energy when together than when separate). Then, while bound
to the catalyst, multiple things can happen to cause a chemical
reaction -- such as other molecules attaching, or the catalyst acting
on the target molecule, etc.
Now let me explain how a nucleic acid molecule can have catalytic
activity: In the case of a nucleic acid enzyme (RNA or DNA enzyme),
the base "rungs" of the RNA serve as the active sites (the
chemically-active part(s) of the molecule) on the surface of the
enzyme. The bases also interact with each other as the molecule folks
around and onto itself, which determines the shape that the enzyme
folds into. These unpaired bases are the key to the enzyme's shape and
to its chemical properties (and therefore, also key to its catalytic
activity).
Next, let me explain the importance of single-stranded nucleic acids
for enzymes: If the nucleic acid were double-stranded, these rungs
would be shielded and the configuration of the molecule would be
severely constrained. Double-stranded RNA (dsRNA) or DNA (dsDNA),
thus, would have little or no catalytic activity. Now, we can make
some guesses as to why ribozmes (RNA enzymes) are common, but
deoxyribozymes (DNA enzymes) only exist in the lab. First, it turns
out dsRNA does not bind very tightly -- it denatures (separates) much
more easily than dsDNA. Thus, single-stranded RNA (which is needed for
a ribozyme) is less energetically favored (that's a thermodynamic way
of of saying it's more rare) than single-stranded DNA. It's harder for
life's functions to develop based on rare molecules than it is on
abundant ones, so this is an argument for RNA over DNA for enzymes.
Along the same lines, cells have defense-mechanisms such as enzymes
that actively try to find and break down DNA. Foreign DNA, or DNA
floating in the cytoplasm might be a threat to the cell. In contrast,
RNA is used routinely in the cell, and is not so aggressively
attacked.
A secondary factor involves the physics of RNA and DNA as well -- how
stiff each molecule is: There is also an argument to be made about the
"radius of gyration" (the "persistence length" is also related) of RNA
and DNA. These basically refer to how 'stiff' a polymer chain is --
the more flexible the chain is, the more freedom it has in bending and
folding. A chain that is more flexible (a shorter persistence length)
would be able to adopt more configurations, and therefore might be a
more efficient catalyst. In simpler terms, it's easier to make a ball
of string than a ball of tree-trunk. There is some research published
that explores this hypothesis, but I think the concept is not
well-established yet.
Hope this helps,
Burr
You are asking how a ribozyme might be a better catalyst than an enzyme.
RNA is single stranded and has a 2 prime OH (hydroxyl), which is a highly
reactive. The ribozyme works by cleaving off the 5 prime end of the
messenger RNA so that it is inactivated and the gene cannot be expressed.
DNA is double stranded and has a 2 prime H (hydrogen).
DNA is used as a template to make a protein, which is the enzyme product
(DNA>RNA> Protein; replication>transcription>translation).
RNA can react and make structural changes faster to changes in the
environment than DNA.
Judy Luke
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Update: June 2012
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