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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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