Hydrogen Bonding in DNA-RNA Hybrids

Why are hydrogen bondings in DNA-RNA hybrids weaker than hydrogen bonds between two strands of DNA or two strands of RNA?

Hydrogen bonding is a crucial factor in the stability and function of nucleic acids, such as DNA and RNA. The hydrogen bonds in DNA-RNA hybrids, which occur when RNA hybridizes with a DNA template during processes like transcription, are generally weaker compared to hydrogen bonds between two DNA strands or two RNA strands. This difference in bond strength arises due to various structural and chemical factors.

1. Base pairing: Nucleic acids are composed of a series of nucleotide bases, which include adenine (A), thymine (T), cytosine (C), guanine (G) in DNA, and adenine (A), uracil (U), cytosine (C), guanine (G) in RNA. In the case of DNA, base pairing occurs between A and T, and between C and G, where two or three hydrogen bonds are formed respectively. However, in the case of DNA-RNA hybrids, base pairing occurs between A and U, and between C and G, leading to the formation of weaker hydrogen bonds due to the presence of uracil instead of thymine. The A-U base pair forms two hydrogen bonds, while the C-G base pair still forms three hydrogen bonds

2. Stacking interactions: Nucleic acid strands have a tendency to stack together due to favorable pi-pi stacking interactions between adjacent bases. In the case of DNA or RNA, the stacking interactions contribute significantly to the overall stability of the molecule. However, in DNA-RNA hybrids, the presence of RNA disrupts the stacking interactions with DNA, reducing the overall stability. The different sugar moieties (deoxyribose in DNA vs. ribose in RNA) and structural differences in the backbone of RNA can cause distortions in the stacking interactions, further weakening the hybrid’s stability

3. Strand flexibility: DNA and RNA molecules have different conformations and structural flexibility. DNA molecules typically adopt a more stable and rigid double helix structure. The presence of RNA within the DNA-RNA hybrid introduces flexibility due to the ribose sugar’s 2′-OH group and the presence of an extra hydroxyl group on the ribose sugar compared to DNA. This flexibility may disturb the alignment and precise positioning of the hydrogen bonding between the strands, leading to weaker interactions

In summary, hydrogen bonds in DNA-RNA hybrids are weaker due to the specific base pairing interactions between A-U and C-G, reduced stacking interactions caused by structural differences between DNA and RNA, and the inherent flexibility of RNA. These factors collectively contribute to the weaker stability of hydrogen bonding in DNA-RNA hybrids compared to hydrogen bonds between two DNA or two RNA strands

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