Genetic Engineering

Why DNA is more stable than RNA?

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2010-01-07 09:23:10
2010-01-07 09:23:10

This is an interesting question you pose, and is one that has been widely

studied over the last 50 years. The structural differences between RNA and

DNA are well understood, though there is still some debate surrounding the

dominant energetics underlying these nucleic acid interactions. This is a

complicated issue, and in the interest of brevity I抦 assuming you have

some general knowledge that I抣l skip over. To address the differences in

thermostability, we have to understand the chemical and structural

differences of DNA versus RNA then the energetic consequences of these


First, let us address the problem of helix formation; both RNA and DNA have

comparable folding mechanisms, that is the formation of base pairing

interactions with a second strand (or same-strand in the case of hairpin

formation), which (1) involves hydrogen-bond formation between opposing

strands, (2) stacking of base pairs on top of one another, (3) reducing

conformational freedom of the phosphodiester backbone.

The first component, base-pairing through hydrogen-bonding interactions may

not be an important factor in comparing DNA versus RNA. In terms of the

individual purines and pyrimidines, the only difference is found in

comparing uracil with thymine (which bears a 5� methyl group lacking in

uracil). This is known to contribute only a small fraction of the total

energy of base-pairing, adding slightly MORE energy to a DNA dA:dT base

pair compared to an RNA A:U base pair. We can ignore this as the primary

source of the high relative thermostability of RNA.

The second and third components are interlinked, since it抯 the

conformation of the phosphodiester backbone that ultimately determines the

relative orientation of one plane of paired nucleotide bases relative to

the nearest neighbor base pairs. For a given nucleotide in either a DNA or

RNA strand, there are no fewer than 6 degrees of freedom (rotatable bonds),

counting two for each phosphate-oxygen, one to the C5� carbon, one between

C5� and C4�, one between the C3� and the oxygen on the phosphate of the

next nucleotide (that抯 five), and finally rotation of the purine/pyridine

base relative to the C1� of the ribose or deoxyribose sugar. In the case

of non-base paired, single-stranded RNA or DNA, all six of these bonds are

freely rotatable which makes these polymers extremely flexible. In order

to become double-stranded, every nucleotide must adopt a single 損referred�

conformation, which requires that all six of these rotatable bonds be fixed

into a single orientation. This is a VERY unfavorable process in terms of

the energetics of forming a double-stranded DNA or RNA, but is largely the

same process for both molecules.

The only other major difference between RNA and DNA is the detailed shape

of the double-helix, A-form for RNA and predominantly B-form for DNA

(please refer to your textbooks or to any of the references below for

additional detail). RNA has never been observed to take on a B

double-helix; the presence of that 2�-OH almost exclusively locks the

ribose into a 3�-endo chair conformation, eliminating the possibility of a

stable B-helix. However, the deoxyribose sugar may alternate between

2�-endo and 3�-endo conformations, allowing DNA to switch between B-form

and A-form under the right circumstances. Note that hybrids of DNA:RNA

(one strand of each in a double-helix) adopt an A-form conformation. (To

better understand the differences in allowable sugar puckers, you might

wish to return to your organic chemistry ball-and-stick models).

The B-form of DNA (in the presence of physiological Na+ or K+) is found at

high relative humidity; large numbers of water molecules are tightly bound

(to the tune of almost 1:1 water/nucleotide). By comparison, it has been

shown that A-form RNA and A-form DNA both are dehydrated somewhat;

measurements of 75% the number of tightly bound water molecules compared to

B-form DNA are commonly cited. There is a distinct difference between

tightly bound water and bulk solvent that will have profound energetic

consequences. In fact, by putting DNA into a dehydrating medium (such as

low salt and high concentrations of ethanol), one can drive the

interconversion of B-form DNA into A-form. Curiously, high salt (>2.5 M

NaCl) and high concentrations of ethanol will drive B-form to Z-form (a

left-handed helix) for DNA, and at elevated temperatures for RNA as well.

The source of these effects are largely Coulombic (charge-charge

interactions) in nature, having to do with the unfavorable interactions

between adjacent phosphates on the backbone and the ability of solvent

composition to diminish (high salt/high humidity) or maximize (low salt/low

humidity) these unfavorable interactions, the details of which are

unapproachably complicated for our discussion.

There are important structural differences between A-form and B-form

helices that we must consider, notably in the diameter of the duplex, the

number of base pairs per turn, the tilt of paired bases relative to the

helical axis, and the solvent accessibility of major and minor grooves. Of

these factors, it is the relative orientation and overlap of

nearest-neighbor base pairing interactions that, though only subtly

different, have contribute to the observed differences in thermostability

of RNA and DNA.

I抳e touched on a few important driving forces governing the transition

between duplex and single-stranded nucleic acids, and some of the potential

STRUCTURAL differences in these interactions between RNA and DNA. In terms

of the relevant energetic contributions, the stacking of base pairs, one

above the other, plus the hydrogen bonds between bases provide the

stabilizing enthalpy of the helix, adding substantial energy stabilizing

the duplex when summed over the length of the DNA/RNA. Both cross-strand

and same-strand van der Waals interactions among bases are important; the

magnitude of these favorable interactions are slightly different for RNA

(more stable) than for DNA; these small differences become large when

summed over many base pairs. The charged phosphate groups repel one

another by Coulomb抯 law of repulsion between like charges, an

enthalpically unfavorable interaction. As mentioned above, the formation

of a double-helix results in a significant reduction in the conformational

degrees of freedom, which is entropically unfavorable in an equally big

way, and are also subtly different in A-form versus B-form.

In total, the single-strand to double-strand transition for both DNA and

RNA is enthalpically favors the helix and entropically favors

single-stranded conformation. For RNA, deltaH ~ 40 kJ mol-1/base pair and

deltaS ~ 105 J K-1 mol-1/base pair (note the entropy is a function of

temperature). For DNA, deltaH ~ 35 kJ mol-1/base pair and deltaS ~ 90 J

K-1 mol-1/base pair. These are VERY large and OPPOSITE driving forces.

In terms of the free energy, the balance of these interactions, we observed

a higher melting temperature of RNA relative to the same sequence in DNA

under normal conditions. The dominant source of this slightly higher

energy for RNA is generally attributed to modestly better base-stacking

energy in the A-form conformation. The precise nature of the molecular

driving forces remain an active area of research. Experimentally, one

observes very little difference in thermostability between RNA:DNA

double-helix compared to an all RNA double-helix, consistent with the

theory that the source of thermostability is due largely the result of

A-form versus B-form conformational differences, not strictly differences

in ribose versus deoxyribose chemistry.

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as DNA is more stable than RNA .So,RNA gets easily hydrolysed easily by hydrolysing phosphodiester bond.

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RNA is shorter than DNA because it is less stable than DNA due the presence of hydroxides.

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DNA is more stable form then RNA b/c DNA is present in double helix form & is highly super coiled which make it more stable and carries genetic information from parents to off springs.

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DNA is more stable than RNA. DNA is double-stranded and forms a double helix. RNA is usually single-stranded and folds back on itself to form stem-loop structures. RNA has 2'-OH group that can participate in intramolecular reactions, facilitating hydrolysis.

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