RNA and DNA Structure

The nucleotides forming RNA or DNA molecules are linked together in phosphodiester bonds with sugar-phosphate repeating units. The esters are directionally linked between the 3 -hydroxyl 

The predictable nature of DNA and RNA base pairing make their interactions the most defined of any biological system. The specific affinity of one strand for its complementary 

This specific base-pairing capability of oligonucleotides defines the structure of 

Unlike the double-stranded nature of DNA, RNA molecules usually occur as single strands. This does not mean they are unable to base-pair as DNA can. Complementary regions within an RNA molecule often base-pair and form complex tertiary structures, even approaching the three-dimensional nature of proteins. Some RNA molecules, such as transfer RNA (tRNA) possess several helical areas and loops as the strand interacts with itself in complementary sections. Other hybrid molecules such as the enzyme RNase P contain protein and RNA portions. The RNA part is highly complex with many circles, loops, and helical regions creating a convoluted structure. 

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To modify the unique chemical groups on nucleic acids, novel methods have been developed that allow derivatization through discrete sites on the available bases, sugars, or phosphate groups (see Chapter 1, Section 3 for a discussion of RNA and DNA structure). These chemical methods can be used to add a functional group or a label to an individual nucleotide or to one or more sites in oligonucleotide probes or full-sized DNA or RNA polymers. 

The 2 -chloro and 2 -bromo congeners of either 748 (FIAC) or 758 (FMAU) are more cytotoxic than FIAC and FMAU, suggesting that these chloro and bromo nucleosides, in contrast to the 2 -fluoro compounds, are comparatively better substrates for deoxycytidine kinase of human lymphocytes than the substrates for viral-specific thymidine kinase. The disposition of the 2 -fluoro group may also be important from the biological viewpoint. It should be noted that the structural difference between RNA and DNA is at the 2 -position. The ribo type of analog (738) of FIAC is 10 times less effective in suppression of HSV replication than is FIAC. Thus Fox, and Watanabe and coworkers concluded that the 2 - up fluorine disposition and the species of the substituent at C-5 are the two important factors influencing antiviral activity. Nevertheless, the mechanism of action of 2 -deoxy-2 -fluorocytidine (737) on certain herpes viruses, including HSV-1... 

The structures of DNA and RNA are similar in that each has a sugar-phosphate backbone with one organic base bound to each sugar. However, there are four distinct differences between RNA and DNA ... 

NRTls are structural analogues of the natural nucleotides that form the building blocks of RNA and DNA in human cells. Their use as part of HAART has dramatically modified the natural history of HIV infection. They, however, cause a range of drag- or tissue-specific toxicides zidovudine (AZT) causes myopathy zalcitabine (ddC), didanosine (ddl), and lamivudine (3TC) cause neuropathy stavudine (d4T) causes neuropathy or myopathy and lactic acidosis (Dalakas 2001). During phase 1 and 11 trials, the dose-limiting toxicity of didanosine, zalcitabine, and stavudine was identified as peripheral neuropathy (Dalakas 2001). 

We have discussed in a general way the nature of animal viruses in the first part of this chapter. Now we discuss in some detail the structure and molecular biology of a number of important animal viruses. Viruses will be discussed which illustrate different ways of replicating, and both RNA and DNA viruses will be covered. One group of animal viruses, those called the retroviruses, have both an RNA and a DNA phase of replication. Retroviruses are especially interesting not only because of their unusual mode of replication, but because retroviruses cause such important diseases as certain cancers and acquired immunodeficiency syndrome (AIDS). 

The nucleus contains a large number of proteins other than histones. These so-called nonhistone proteins may or may not be tightly associated with the chromosomes. For example, the nucleus contains enzymes associated with the synthesis of RNA and DNA these are nonhistone proteins, but they are not part of the structure of chromosomes. One group of nonhistone proteins are the high mobility group (HMG) proteins, named for their rapid movement on polyacryl-amide gel electrophoresis. The HMG proteins, but not histone HI, are associated with the chromatin that is most active in RNA synthesis. 

Not all the cellular DNA is in the nucleus some is found in the mitochondria. In addition, mitochondria contain RNA as well as several enzymes used for protein synthesis. Interestingly, mitochond-rial RNA and DNA bear a closer resemblance to the nucleic acid of bacterial cells than they do to animal cells. For example, the rather small DNA molecule of the mitochondrion is circular and does not form nucleosomes. Its information is contained in approximately 16,500 nucleotides that func-tion in the synthesis of two ribosomal and 22 transfer RNAs (tRNAs). In addition, mitochondrial DNA codes for the synthesis of 13 proteins, all components of the respiratory chain and the oxidative phosphorylation system. Still, mitochondrial DNA does not contain sufficient information for the synthesis of all mitochondrial proteins most are coded by nuclear genes. Most mitochondrial proteins are synthesized in the cytosol from nuclear-derived messenger RNAs (mRNAs) and then transported into the mito-chondria, where they contribute to both the structural and the functional elements of this organelle. Because mitochondria are inherited cytoplasmically, an individual does not necessarily receive mitochondrial nucleic acid equally from each parent. In fact, mito-chondria are inherited maternally. 

Shapiro (2000) draws our attention to another type of problem the homopolymer problem in biogenesis. Many biogenesis hypotheses presuppose the spontaneous formation of polymeric organic replicators which were formed from a mixture of inorganic compounds these replicators consist of subunits of a known chemical species. Their structure involves a backbone which is bonded to information-transmitting residues. As we shall discuss in Sect. 6.7, not only RNA and DNA, but also proteins and peptide nucleic acids (PNA) have been suggested as possible information transmitters. Shapiro rightly considers that until now, not... 

Figure 1.49 The structures of the common purine bases of RNA and DNA. The associated sugar groups are bound in N-glycosidic linkages to the N-9 position.

Figure 3.3 Chemical structure of (a) ribose and (b) 2 -deoxyribose, the nucleotide pentoses found in RNA and DNA respectively. The differences in chemical structure are highlighted by the dotted circles...

Nuclease PI is another trizinc enzyme which cleaves the phosphodiester bond in single-stranded RNA and DNA. Protein crystallography has revealed that the structure of the three zinc site is very similar to that... 

Antisense Approach This is a relatively new approach and it requires modifications to oligonucleotides that can bind to RNA and DNA (refer to Appendix 2 for a description of cell structure, genes, DNA, RNA, and proteins). The antisense drugs are used to stop transcriptional (from DNA) or translational (from RNA) pathways from proceeding, and so interfere with the process of disease. 

DNA is one type of nucleic acid. The other type of nucleic acid is called RNA (short for ribonucleic acid). RNA is present throughout a cell. It works closely with DNA to produce the proteins in the body. Table 2.3, on the next page, shows the structures of RNA and DNA. 

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