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INTRODUCTION TO NUCLEIC ACIDS

Nucleic acids are the carriers of genetic information. In all living organisms, the hereditary
information is stored in deoxyribonucleic acid (DNA), which is a molecule formed by the
repetition of nucleotides (making DNA a polymer). There are four different nucleotides in DNA,
which form a universal code for hereditary information. Ribonucleic acid (RNA), the other kind
of nucleic acid, is a related molecule to DNA. It is also a polymer of four nucleotides, three of
which are the same as in DNA while the fourth one is slightly different. It has many functions in
cells, notably acting as the intermediate between DNA and proteins. Some viruses even store
their genome in the form of an RNA molecule rather than DNA.

PURINES AND PYRIMIDINES

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Purines and pyrimidine’s are both organic compounds that take part in the synthesis of DNA and
RNA, therefore they are called as the building blocks of the genetic material – DNA and RNA.
They are nitrogenous bases that make up the two different nucleotides in DNA and RNA.
Purines (adenine and guanine) are two-carbon nitrogen ring bases while pyrimidine’s (cytosine
and thymine) are one-carbon nitrogen ring bases.
Given below in a tabular column are the differences between Purines and Pyrimidine’s.
Purines Pyrimidine’s
Purine is a heterocyclic aromatic organic Pyrimidine is a heterocyclic aromatic
compound composed of a pyrimidine ring fused organic compound that is composed of
with imidazole ring. carbon and hydrogen.

It comprises adenine and guanine as It comprises Cytosine, thymine, uracil as

nucleobases.
It consists of two hydrogen-carbon rings and
four nitrogen atoms
The melting point of purine is 214 °C
Catabolism results in the production of uric
acid
nucleobases
It consists of one hydrogen-carbon ring and
two nitrogen atoms
The melting point of pyrimidine is 20-22 °C
Catabolism produces carbon dioxide, beta-
amino acids and ammonia
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NUCLEOTIDES
Nucleotides are the building blocks of nucleic acids: they are the monomers which, repeated
many times, form the polymers DNA and RNA. Nucleotides are composed of a five-carbon
sugar covalently attached to a phosphate group and a base containing nitrogen atoms. Figure 1
shows the structure of the nucleotides making up nucleic acids.

Figure 1 | The chemical structure of a nucleotides. A nucleotide comprises a five-carbon sugar

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molecule: deoxyribose in DNA (A) and ribose in RNA (B). The carbon atoms on the sugar
molecule are numbered in red. Deoxyribose (A) is different from ribose (B) in that it lacks an –
OH group at carbon 2’. The 5’-carbon atom is attached to a phosphate group (here a
monophosphate in orange) and the 1’-carbon is attached to a base (blue).
The main difference between nucleotides from DNA and those from RNA is the nature of the
sugar. Nucleotides making up RNA (Figure 1B) contain ribose, making them ribonucleotides. In
DNA, however, the sugar lacks an –OH group at the 2’-carbon, making it deoxyribose and the
corresponding nucleotides deoxyribonuleotides. A nucleotide may contain more than one
phosphate at its 5’-carbon, for instance the nucleotide adenosine triphosphate has three, as shown
in Figure 2. When there is no phosphate group, the molecule is no longer called a nucleotide, but
a nucleoside.

Figure 2 | Adenosine triphosphate, often abbreviated to ATP.

NUCLEOTIDES: (Building Blocks Of Nucleic Acids

Basic Structure)
Nucleic acids are polynucleotides—that is, long chainlike molecules composed of a series of
nearly identical building blocks called nucleotides. Each nucleotide consists of a nitrogen-
containing aromatic base attached to a pentose (five-carbon) sugar, which is in turn attached to
a phosphate group. Each nucleic acid contains four of five possible nitrogen-
containing bases: adenine (A), guanine (G), cytosine (C), thymine (T), and uracil (U). A and G
are categorized as purines, and C, T, and U are collectively called pyrimidines. All nucleic acids
contain the bases A, C, and G; T, however, is found only in DNA, while U is found in RNA. The
pentose sugar in DNA (2′-deoxyribose) differs from the sugar in RNA (ribose) by the absence of
a hydroxyl group (―OH) on the 2′ carbon of the sugar ring. Without an attached phosphate
group, the sugar attached to one of the bases is known as a nucleoside. The phosphate group
connects successive sugar residues by bridging the 5′-hydroxyl group on one sugar to the 3′-
hydroxyl group of the next sugar in the chain. These nucleoside linkages are called
phosphodiester bonds and are the same in RNA and DNA
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BASES IN NUCLEIC ACIDS

he nucleotides making up DNA contain one of four nitrogenous bases (i.e. bases that contain
nitrogen atoms). From a chemical perspective, two of those bases are purines, while the other
two are pyrimidines. To each base corresponds a name (e.g. adenine), a nucleoside (e.g.
adenosine) and a one-letter code (e.g. A). This information is included in Table 1.

Table 1 | The four bases of DNA. The ‘R’ represents the deoxyribose covalently attached to the
base to form the nucleoside named in the third row.
As mentioned above, the sugar in RNA is ribose rather than deoxyribose. However, there is
another difference between DNA and RNA in the base composition. RNA contains three of the
bases found in DNA (adenine, guanine and cytosine) but thymine is replaced by the related base,
uracil. The four bases found in RNA, along with the names of their corresponding nucleosides,
are in Table 2.
Table 2 | The four bases of RNA. The ‘R’ represents the ribose covalently attached to the base to
form the nucleoside named in the third row.

3D STRUCTURE OF DNA
DNA is predominantly found as a double helix: two strands of polynucleotides wind about the
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same axis to form a right-handed helix. Each nucleotide provides a ribose and a phosphate to the
backbone. The bases project towards the centre of the helix, away from the surrounding water.
The DNA double helix is shown in Figure 3.

Figure 3 | The double-helical structure of DNA. A. DNA shown as a cartoon. B. DNA shown as
sticks, with a cyan cartoon highlighting the sugar-phosphate backbone. Green: base pair; grey:
carbon; red: oxygen; blue: nitrogen; white: hydrogen; orange: sulphur.

DNA can adopt slightly different kinds of 3D structure, but the majority of the DNA inside a cell
at any given point will have the structure shown in Figure 3, called B-DNA. It has 10 base pairs
per helical turn and a rise of 3.4Å per base pair.
WATSON-CRICK BASE PAIRING
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He double helix shown in Figure 3 can only accommodate two kinds of base pairs, due to the
geometry of the bases. Adenine and thymine bases always pair with each other while guanine
and cytosine bases always pair with each other. This kind of pairing, called Watson-Crick base
pairing, is mediated by hydrogen bonds between the two bases of a pair, as shown in Figure 4.

Figure 4 | A. Watson-Crick base pairing between deoxyriboadenosine monophosphate and

deoxyribothymidine monophosphate. B. Watson-Crick base pairing between deoxyribocytidine
monophosphate and deoxyribo guanosine monophosphate. Only the name of the base is given
below each nucleotide. The hydrogen bonds are shown by orange dotted lines. Grey: carbon; red:
oxygen; blue: nitrogen; white: hydrogen; orange: sulphur.
DIRECTIONALITY OF DNA
A strand of DNA is the result of the polymerisation of several nucleotides, with the backbone
formed by the deoxyribose sugars and the phosphate groups. Each nucleotide residue (i.e. a
nucleotide within a strand of DNA) contains a phosphate group covalently attached to the 5’-
carbon of its deoxyribose, but also has its deoxyribose 3’-carbon covalently attached to the
phosphate of the next nucleotide residue in the strand. The only exception is the final nucleotide,
which does not have a phosphate at its 3’-carbon (of the deoxyribose), but rather a free –OH
group. We define this end of the strand as the 3’-end. The very first nucleotide residue, on the
other hand, has a free phosphate group attached to its 5’-carbon. We define that end of the strand
as the 5’-end. DNA is always read from the 5’-end to the 3’-end, as shown in Figure 5.
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Figure 5 | The directionality of DNA. A stretch of 3 nucleotide residues is shown with their 5’-
and 3’-carbons numbered. In red are the 5’-end (characterised by a free phosphate group) and the
3’- end (characterised by a free –OH group).
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Note that, when studying DNA in the lab, it is common to remove the phosphate at the 5’-end,
therefore many experimentally determined structures will actually show an –OH group rather
than a phosphate at the 5’-end.
HOW DOES THE SRUCTURE OF RNA DIFFER FROM THAT OF DNA?
As mentioned above, RNA is made of ribonuleotides rather than deoxyribonucleotides: the 2’-
carbon of its ribose is covalently attached to an –OH group. Furthermore, RNA contains the base
uracil instead of thymine. The other main difference between RNA and DNA is that RNA is
often single-stranded and does not form the regular double-helical structure of DNA. However, it
is quite common for a single RNA strand to fold on itself and to form complex 3D structures,
with some helical character. When that is the case, the 3D structure is often stabilised by the
same Watson-Crick base-pairing as in DNA, although some deviations may be allowed (often
disrupting helices). The directionality of RNA, however, is the same as that of DNA: the
sequence is read from the 5’-end to the 3’-end.
RIBONUCLEIC ACID (RNA)
RNA is a single-stranded nucleic acid polymer of the four nucleotides A, C, G, and U joined
through a backbone of alternating phosphate and ribose sugar residues. It is the first intermediate
in converting the information from DNA into proteins essential for the working of a cell. Some
RNAs also serve direct roles in cellular metabolism. RNA is made by copying the base sequence
of a section of double-stranded DNA, called a gene, into a piece of single-stranded nucleic acid.
This process, called transcription (see below RNA metabolism), is catalyzed by an enzyme called
RNA polymerase.

CHEMICAL STRUCTURE
Whereas DNA provides the genetic information for the cell and is inherently quite stable, RNA
has many roles and is much more reactive chemically. RNA is sensitive to oxidizing agents such
as periodate that lead to opening of the 3′-terminal ribose ring. The 2′-hydroxyl group on the
ribose ring is a major cause of instability in RNA, because the presence of alkali leads to rapid
cleavage of the phosphodiester bond linking ribose and phosphate groups. In general, this
instability is not a significant problem for the cell, because RNA is constantly being synthesized
and degraded.

Single-stranded RNAs are flexible molecules that form a variety of structures through internal
base pairing and additional non-base pair interactions. They can form hairpin loops such as those
found in transfer RNA (tRNA), as well as longer-range interactions involving both the bases and
the phosphate residues of two or more nucleotides. This leads to compact three-dimensional
structures. Most of these structures have been inferred from biochemical data, since few
crystallographic images are available for RNA molecules. In some types of RNA, a large number
of bases are modified after the RNA is transcribed. More than 90 different modifications have
been documented, including extensive methylations and a wide variety of substitutions around
the ring. In some cases these modifications are known to affect structure and are essential for
function.
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TYPES OF RNA
MESSENGER RNA (mRNA)

Messenger RNA (mRNA) delivers the information encoded in one or more genes from the DNA
to the ribosome, a specialized structure, or organelle, where that information is decoded into
a protein. In prokaryotes, mRNAs contain an exact transcribed copy of the original DNA
sequence with a terminal 5′-triphosphate group and a 3′-hydroxyl residue. In eukaryotes the
mRNA molecules are more elaborate. The 5′-triphosphate residue is further esterified, forming a
structure called a cap. At the 3′ ends, eukaryotic mRNAs typically contain long runs of
adenosine residues (polyA) that are not encoded in the DNA but are added enzymatically after
transcription. Eukaryotic mRNA molecules are usually composed of small segments of the
original gene and are generated by a process of cleavage and rejoining from an
original precursor RNA (pre-mRNA) molecule, which is an exact copy of the gene (as described
in the section Splicing). In general, prokaryotic mRNAs are degraded very rapidly, whereas the
cap structure and the polyA tail of eukaryotic mRNAs greatly enhance their stability.

RIBOSOMAL RNA (rRNA)
Ribosomal RNA (rRNA) molecules are the structural components of the ribosome. The rRNAs
form extensive secondary structures and play an active role in recognizing conserved portions of
mRNAs and tRNAs. They also assist with the catalysis of protein synthesis. In the prokaryote E.
coli, seven copies of the rRNA genes synthesize about 15,000 ribosomes per cell. In eukaryotes
the numbers are much larger. Anywhere from 50 to 5,000 sets of rRNA genes and as many as 10
million ribosomes may be present in a single cell. In eukaryotes these rRNA genes are looped
out of the main chromosomal fibres and coalesce in the presence of proteins to form an organelle
called the nucleolus. The nucleolus is where the rRNA genes are transcribed and the early
assembly of ribosomes takes place.
.
TRANSFER RNA (TRNA)

Transfer RNA (tRNA) carries individual amino acids into the ribosome for assembly into the
growing polypeptide chain. The tRNA molecules contain 70 to 80 nucleotides and fold into a
characteristic cloverleaf structure. Specialized tRNAs exist for each of the 20 amino acids
needed for protein synthesis, and in many cases more than one tRNA for each amino acid is
present. The nucleotide sequence is converted into a protein sequence by translating each three-
base sequence (called a codon) with a specific protein. The 61 codons used to code amino acids
can be read by many fewer than 61 distinct tRNAs (as described in the section Translation). In E.
coli a total of 40 different tRNAs are used to translate the 61 codons. The amino acids are loaded
onto the tRNAs by specialized enzymes called aminoacyl tRNA synthetases, usually with one
synthetase for each amino acid. However, in some organisms, less than the full complement of
20 synthetases are required because some amino acids, such as glutamine and asparagine, can be
synthesized on their respective tRNAs. All tRNAs adopt similar structures because they all have
to interact with the same sites on the ribosome
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