Secondary Structure of RNA: Its Importance and Methods of Determination

A molecule of RNA consists of a long chain of subunits, called ribonucleotides. Each ribonucleotide contains one of four possible bases: adenine, guanine, cytosine, or uracil (abbreviated as A,G,C,U respectively). It is this sequence of bases, known as the primary structure of the RNA that distinguishes one RNA from another.

Under normal physiological conditions, a ribonucleotide chain can bend back upon itself, and the bases can hydrogen-bond with one another, such that the molecule forms a coiled and looped structure. The pattern of hydrogen bonding is generally called the secondary structure, while the conformation of the molecule in 3-dimensional space is called the tertiary structure.

.The base-to-base interactions that form the RNA secondary structure are primarily of two kinds — hydrogen bonding between G and C and hydrogen bonding between A and U, as was first described by Watson and Crick in [1953]. (See Figure 1.) In fact, there is evidence of non-Watson-Crick base pairing in such nucleic acids as the tRNAs, but these are considered to derive from the tertiary structure produced by large regions of secondary structure containing Watson-Crick base pairing.

For the sake of simplicity, such base pairing is mostly ignored in this paper. Genetic information, the set of instructions that directs cell maintenance, growth, differentiation, and proliferation, is encoded in DNA molecules. RNA serves two biological purposes: It is the means by which information flows from DNA into the production of proteins, the catalysts and building blocks of cells; it also acts as a structural component of ribosomes and other complexes.

It is the secondary structure, and the resulting tertiary structure, that determine how the RNA will interact and react with other cell components. Work on the determination of RNA secondary structure has been carried out for decades by a number of research groups. The classical approach is direct observation of a molecule’s secondary structure using X-ray crystallography.


More indirect methods involve specific cleavage of the RNA by enzymes called ribonucleases. Much research has gone into the promising approach of computational prediction of secondary structure from knowledge of primary structure. The general method has been to search for configurations of maximum base-pairing or of minimum free energy.

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