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10 Similarities and Differences between RNA and DNA Recognition by Proteins

Thomas A. Steitz


Many DNA and RNA molecules are recognized by proteins that interact preferentially with a specific DNA sequence or a particular RNA molecule. I address here the structural basis by which these proteins recognize their target nucleic acid and show in what ways recognition of RNA and DNA is both similar and different. Sequence-specific DNA-binding proteins interact with duplex DNA that is in B-form. RNA molecules, on the other hand, invariably consist of duplex regions, often stacked one on another, that are A-form, as well as regions of single-stranded loops and bulges, making possible a more complex and richly varied three-dimensional shape than can be assumed by duplex DNA. Presently, the crystallographic and nuclear magnetic resonance (NMR) structural database of proteins complexed with DNA is very large, revealing some patterns and general conclusions about the source of sequence-specific DNA recognition (for reviews, see Steitz 1990; Harrison 1991; Pabo and Sauer 1992). On the other hand, the structural database for RNA-binding proteins, particularly in complex with RNA, is very meager indeed, so that any generalizations made may soon be overturned by the next structure determination of an RNA-protein complex. Nevertheless, some patterns of similarity and difference in the structural basis of nucleic acid recognition by proteins can be seen at this time.

Structural, biochemical, and molecular genetic studies of protein nucleic acid complexes have established at least three important sources of sequence specificity in protein-nucleic acid interactions: (1) Direct hydrogen bonding and van der Waals interaction between protein side chains and the...

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