Chapter Introduction

6: DNA and RNA Structure

173

  • 6.1 The Structure and Properties of Nucleotides

  • 6.2 DNA Structure

  • 6.3 RNA Structure

  • 6.4 Chemical and Thermodynamic Properties of Nucleic Acids

MOMENT OF DISCOVERY

Jamie Cate

When I first started my lab at the Whitehead Institute, my dream was to crystallize the bacterial ribosome and to solve its molecular structure at high resolution. Although a lot had been learned about RNA structure from work on catalytic RNAs and the individual subunits of the ribosome, the possibility of seeing the complete structure of the protein-synthesizing machinery was irresistible.

Working closely with graduate student Steve Santoso, we eventually got one small perfect-looking crystal to grow from a purified ribosome sample. We took the crystal to a synchrotron x-ray beamline and saw the first diffraction pattern indicating that the crystal indeed contained ribosomes. That was so exciting! But just to be sure, we recovered the crystal from the x-ray diffraction apparatus, dissolved it in water, and checked the contents on an agarose gel—and there was the ribosomal RNA, clear as could be.

We figured out how to grow more of those crystals, and eventually we solved the crystal structure of the complete ribosome. Staring in awe at the electron density map, we saw how the RNA helices wove through the molecule like great curving spiral staircases. I felt chills down my spine, realizing I was the first person to see such incredible molecular beauty. This was the culmination of six years of challenging—and at times frustrating—experiments. I felt the sweet joy of success, and also contemplated the many new discoveries that would result from this work.

—Jamie Cate, on determining the molecular structure of the bacterial ribosome

174

Discovered in the nineteenth century, DNA (deoxyribonucleic acid) would be proposed, by the early twentieth century, as the molecule that stores biological information (see Chapter 2). At that time, however, the way in which the particular properties of its molecular structure could produce traits and behaviors in living organisms was unimaginable. By midcentury, hoping to determine how DNA carried genetic messages that are faithfully transmitted to the next generation when cells divide, researchers in several laboratories had made it their goal to solve the molecular structure of DNA. In 1953, James Watson and Francis Crick, at Cambridge University, used x-ray diffraction data obtained by Rosalind Franklin to deduce DNA’s simple and beautiful double-helical structure (Figure 6-1). This landmark discovery, for which Watson and Crick (together with Maurice Wilkins, for his work on the x-ray diffraction) received the Nobel Prize in Physiology or Medicine in 1962, gave rise to all of modern molecular biology. It was immediately apparent to scientists how this unique structure of DNA could allow biological information to be easily and faithfully duplicated and transmitted from generation to generation.

Figure 6-1: Francis Crick’s first drawing of DNA structure. Two base-paired strands of DNA form a helical structure in which the phosphate and sugar groups are on the outside and the bases are on the inside. The helix twists in a right-handed direction.
James Watson
Francis Crick, 1916–2004

Like DNA, RNA (ribonucleic acid) was first isolated in the nineteenth century from the nuclei of cells. Scientists later recognized that RNA is chemically distinct from DNA, because it contains a different kind of sugar in its nucleotide building blocks (see Chapter 3). As described in Chapter 2, ribosomal RNAs (rRNAs) were found to be components of ribosomes, the complexes that carry out protein synthesis. Messenger RNAs (mRNAs) were known to be intermediaries, carrying genetic information from genes to ribosomes. And transfer RNAs (tRNAs) had been identified as adaptor molecules that translate the information in mRNA into a specific sequence of amino acids. We now know that RNA molecules have many other biological functions as well. For example, they comprise the genomes of certain viruses, such as the human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Some RNA molecules have the ability to work as catalysts—a discovery that provided, for the first time, a plausible scenario for the evolution of early life forms based on self-replicating RNA. (The diversity of functional RNAs and their roles in evolution are discussed in Chapters 15 and 16.) In the quest to understand how RNA could perform such a range of functions, researchers have determined the structures of numerous types of RNA molecules and RNA-protein complexes, including the structure of the ribosome itself. Unlike DNA, RNA molecules are almost always single-stranded, and they consist of much shorter chains of nucleotides. They also have a propensity to fold back on themselves, creating many discrete double-helical regions that can assemble into complex three-dimensional structures.

As we will see, there is no single generic structure of DNA or RNA. Rather, there are numerous variations on a common structural theme, resulting from the chemical and physical properties of the polynucleotide chain. Indeed, the structural stability of DNA and the structural diversity of RNA explain why these molecules have evolved to function in all aspects of maintaining and transmitting biological information. In this chapter, we first explore the general properties of nucleotides, then turn to the structures of DNA and RNA. We conclude by looking at the chemical behavior of nucleic acids under biological conditions.