Structural Distinction at the 2' Position Between RNA and DNA Sugars
RNA contains a hydroxyl group (-OH) at the 2' position of its pentose sugar (ribose), while DNA has only a hydrogen atom (-H) at this position (deoxyribose). 1
The Critical Structural Difference
The pentose sugar in RNA is ribose with a 2'-hydroxyl group, whereas DNA contains deoxyribose with a 2'-hydride (hydrogen atom) at the same position. 1 This single structural modification—the presence versus absence of the 2'-OH group—represents the fundamental chemical distinction between these two nucleic acid backbones.
Functional Consequences of the 2'-Hydroxyl Group
Chemical Reactivity and Stability
The 2'-hydroxyl group makes RNA approximately 100,000-fold less stable than DNA under physiological conditions due to its susceptibility to nucleophilic attack. 1
This 2'-OH group favors nucleophilic attack through trans-esterification, where the deprotonated 2'-oxygen attacks the adjacent 3'-phosphorus center, cleaving the 3'-5' phosphodiester bonds. 1
The resulting hydrolysis produces fragments containing 2',3'-cyclic phosphate and 5'-hydroxyl termini. 1
Conformational Impact
A single 2'-hydroxyl group is sufficient to convert B-DNA conformation to A-DNA conformation, demonstrating the profound structural influence of this modification. 2
The 2'-OH groups stabilize RNA hairpin structures through intramolecular hydrogen bonding networks with sugars, bases, and phosphates. 3
These hydroxyl groups project into the minor groove and participate in hydrogen bonding that can involve adjacent nucleotides or groups on opposite sides of structural loops. 3, 4
Thermodynamic Considerations
The free energy contribution of the 2'-hydroxyl group to conformational equilibrium is consistently measured at ΔΔG = 1.75 ± 0.15 kJ/mol per sugar moiety. 5
This thermodynamic "driving force" explains RNA's tendency to adopt the N(C3'-endo) sugar puckering domain, while DNA predominantly adopts the S(C2'-endo) conformation. 5
The 2'-OH effect on stability is independent of and comparable in magnitude to the C-5 methyl group effect (thymine vs. uracil), with both contributing equally large effects on nucleic acid stability. 6
Common Pitfalls to Avoid
Do not confuse the 2' position modification with other structural differences between RNA and DNA (such as thymine vs. uracil at the base level)—the 2'-hydroxyl is specifically a sugar modification. 1
Recognize that this single hydroxyl group has cascading effects on RNA stability, three-dimensional structure, and susceptibility to hydrolysis under various pH conditions and in the presence of metal ions. 1
The 2'-OH groups are particularly vulnerable to degradation under both alkaline (pH > 7) and acidic (pH < 3) conditions, making RNA handling significantly more challenging than DNA in laboratory and therapeutic applications. 1