What Causes DNA to Be More Chemically Stable Than RNA?

DNA is significantly more chemically stable than RNA, which is essential for its role as a permanent genetic archive. This difference in stability is primarily due to a single chemical difference in their sugar backbones.

The 2'-Hydroxyl (OH) Group in RNA

Both DNA and RNA have a 5-carbon sugar, but they differ at the 2' (two-prime) carbon position on the sugar ring:

• RNA's sugar is Ribose: It has a hydroxyl (OH) group at the 2' position.
• DNA's sugar is Deoxyribose: It has only a hydrogen (H) atom at the 2' position. The "deoxy" in its name literally means it is missing an oxygen.

Why This Matters

The 2'-hydroxyl group on RNA's ribose sugar is chemically reactive. This (OH) group can act as a nucleophile and attack the adjacent phosphodiester bond in the RNA backbone. This process, known as self-hydrolysis, causes the RNA strand to easily break itself apart, especially in alkaline (basic) conditions. DNA, lacking this reactive 2'-OH group, is not susceptible to this form of self-degradation and remains a stable long-chain polymer.

Other Stabilizing Factors

• Structure: DNA's double-stranded helix structure provides physical protection for the bases on the inside. Most RNA is single-stranded, leaving its bases more exposed to enzymes and chemical damage.
• Base: DNA uses Thymine (T), while RNA uses Uracil (U). Cytosine (C) can naturally decay into Uracil. In DNA, repair enzymes can easily spot a 'U' as an error and fix it. In RNA, 'U' is a normal base, so this form of informational decay cannot be as easily repaired.