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Nucleic Acids and their Structure

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 poly-
mer 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.
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

molecule: deoxyribose in DNA (A) and ribose in RNA (B). The carbon atoms on the sugar
moleculeare 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, how-
ever, 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.
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Figure 2 | Adenosine triphosphate, often abbreviated to ATP.

Bases in nucleic acids

The nucleotides making up DNA contain one of four nitrogenous bases (i.e. bases that contain nitro-
gen 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.

Adenine Guanine Cytosine Thymine

Deoxyadenosine Deoxyguanosine Deoxycytidine Deoxythymidine
A G C T
Purines Pyrimidines

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 fourbases
found in RNA, along with the names of their corresponding nucleosides, are in Table 2.
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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.

Adenine Guanine Cytosine Uracil

Adenosine Guanosine Cytidine Uridine
A G C U

Purines Pyrimidines

3D structure of DNA
DNA is predominantly found as a double helix: two strands of polynucleotides wind about the 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.

Two bases (each from a different strand) come together to form a base pair, shown in green in Figure
3A. A base pair is held together by hydrogen bonds between the two bases (Watson-Crick base pairing
explained below).
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.
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Watson-Crick base pairing
The 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 cytosinebases
always pair with each other. This kind of pairing, called Watson-Crick base pairing, is mediatedby
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
mono- phosphate and deoxyriboguanosine 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.

Note that an AT base pair is only held by two hydrogen bonds whereas a CG base-pair has three,
making the latter more stable.
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 withina
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 attachedto 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).

Properties of DNA (Deoxyribonucleic acid)

1. DNA is made up of two helical strands that are coiled around the same axis. If coiled from right it is
known as right-handed helices DNA and if coiled from left then it is known as left-handed helices.
However, the right-handed helices DNA is the most stable and thus the structure of it is to be referred
to as the standard.
2. The two chains of helices run antiparallel to each other. Thus, one strand runs 5’ to 3’ and another
strand runs from 3’ to 5’.
3. Both the strands denature on heating and can renature or say hybridize on cooling. However, the
temperature on which these strands are separately permanently is referred to as melting temperature
and varies according to the specific sequence of DNA.
4. For instance, the region of higher concentration of C-G has a higher melting temperature cause these
bases are bonded with three hydrogen bonds, which require more energy to break than the region of
higher concentration A-T which are bonded only with two hydrogen bonds.
5. These nitrogenous bases store genetic information and thus encode for amino acids which give rise
to proteins.
Major and Minor Grooves of the DNA
 As a result of the double helical nature of DNA, the molecule has two asymmetric grooves. One
groove is smaller than the other.
 This asymmetry is a result of the geometrical configuration of the bonds between the phosphate,
sugar, and base groups that forces the base groups to attach at 120 degree angles instead of 180
degree.
 The larger groove is called the major groove, occurs when the backbones are far apart; while the
smaller one is called the minor groove, occurs when they are close together.
 Since the major and minor grooves expose the edges of the bases, the grooves can be used to tell
the base sequence of a specific DNA molecule.
 The possibility for such recognition is critical, since proteins must be able to recognize
specific DNA sequences on which to bind in order for the proper functions of the body and cell to
be carried out.
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Types of DNA on the basis of forms
1. B-form
 The standard structure of DNA that is commonly known, was described by Watson and Crick and
is a right-handed double helix.
 The double-helical chains run antiparallel to each other, one running from 5’ to 3’ and another
running from 3’ to 5’ and are joined together via complementary nitrogenous base pairing.
 Based upon Chargaff’s rules, bases coherent with another, only when one purine of one strand pairs
with one pyrimidine of another strand. A with T and G with C
 The pair formed is a keto base pair, with an amino base, a purine with a pyrimidine.
 The two strands of the DNA molecule are plectonemic coil which means that these two strands are
coiled around the same axis and are intertwined with each other.
 The consequence of this plectonemic coil is that these two strands can’t be separated without the
DNA rotating.
 The distance between the base pairs is 0.34 nm. One turn of the helix contains 10 base pairs with a
length of 3.4 nm.
 This form of DNA is 1.9 nm in diameter, which means the width of the helix is 1.9 nm.
 The wide and shallow major groove of 2.2 nm, making it easily assessable to proteins, and narrow
and minor groove of 1.1 nm.
2. A-form
 The major difference between the A and B forms of DNA is the conformation of the deoxyribose
sugar ring. For B form, it is in the C2 endo-conformation, while in A form it is in the C3 endo-
conformation.
 Another important difference between A and B-form is the arrangement or placement of
nitrogenous base pairs within the duplex.
 In B-form, the base pairs are almost in the center over the helical axis, whereas in A-form, the base
pairs are diverted away from the central axis towards the major groove.
 The distance between two base pairs is 0.29 nm. One turn of the helix contains 11 base pairs with
a length of 2.8 nm
 Shorter than B-form of DNA. However, the helical width is 2.3 nm which is more than B-form.
 Narrow and deep major groove and wide and shallow minor groove.
 This form of DNA is favored by low hydration and by repeating units of purines or pyrimidines.
3. Z-form
 It is a left-handed helix and is a very different structure when compared with the A and B-form.
 This form of DNA can form when the DNA is in alternating purines-pyrimidines sequences.
 The backbone is not a smooth helix but an irregular zig-zag, which is resulted from alternating
sequences of purines and pyrimidines.
 The B form DNA can take the Z form when proteins are bound to DNA in one helical conformation
and force the DNA to adopt a different conformation.
 This adoption happens at the G nucleotide, the sugar in this form is of C3 endoconformation and
the guanine base is in the synconformation.
 The result of which places the guanine back over the sugar ring, which is unusual than the B and A
form.
 It is long and thin than the B and A forms.
 The helical width is 1.8 nm, being the smallest among the three forms.
 The distance between the base pairs is 0.37 nm. One turn of the helix contains 12 base pairs with a
length of 4.56 nm.
 The major groove is flat and the minor groove is narrow and deep.
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Figure 6 - Types of DNA based on forms

Types of DNA on the basis of location

1. Nuclear DNA
 As the name suggests, these DNAs are located inside the nucleus organized in the chromosome.
 These chromosomes are 23 pairs in humans and are linear with open ends and contain 3 billion
nucleotides.
 Nuclear DNA houses genes that are transcribed into mRNA and ultimately translated to proteins,
that are necessary for the functioning and maintaining the integrity of the cell.
 It is inherited from both parents, so this is diploid and considered unique to each individual except
for identical twins.
 It is usually present in two copy numbers per cell
2. Mitochondrial DNA
 It is located inside the mitochondria.
 It is small and circular in structure
 It is inherited only from the mother, so is a haploid.
 It is present in a much higher copy number. i.e., 100-10,000 per cell.
 It has only 16,500 base pairs and encodes proteins that are specific for mitochondria. These proteins
are vital for producing energy.
 Mitochondrial DNA encoded proteins also play a pivotal role during intracellular protein transport.
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Functions of DNA (Deoxyribonucleic acid)
1. DNA stores complete genetic information that requires to specify an organism.
2. It is the source of information that is needed in order to synthesize cellular proteins, and other
macromolecules required by an organism.
3. It is responsible for identifying and determining the individuality of the given organism.
4. It can also be taken as a targeted element during the diagnosis of a particular disease.
5. It can replicate to give rise to two daughter cells and transfer one copy to the daughter cells during
cell division. Thus, maintaining the genetic materials from generation to generation.
How does the structure 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 in-
stead 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.
RNA (Ribonucleic acid) is a single-stranded nucleic acid molecule and made up of ribonucleotides.
 A ribose nucleotide in the chain of RNA consists of a ribose sugar, phosphate group, and a base.
 In each ribose sugar, one of the four bases is added: Adenine (A), Guanine (G), Cytosine (C), and
Uracil (U).
 The base is attached to a ribose sugar with the help of a phosphodiester bond. As RNA comprises
many ribose nucleotides, the length of the chains of nucleotides can vary according to their types
or their functions.
 RNA thus differs from DNA, on the type of sugar used to make the molecule and replacement of
base Thymine in DNA with Uracil in RNA. Additionally, DNA is a double-stranded molecule
whereas RNA is a single-stranded molecule.
Properties of RNA
1. RNA is a single-stranded molecule and not a double helix, one of the consequences of this, is that
RNA can form a variety of three-dimensional molecular complexes than DNA.
2. RNA has ribose sugar in its nucleotides, rather than deoxyribose. These two sugars differ from each
other in the presence or absence of an Oxygen atom.
3. Ribose sugar is also a cyclical structure consisting of 5 Carbon and one Oxygen just like DNA. But
the major difference is the presence of extra OH group in 2’ Carbon of ribose which is absent in
deoxyribose sugar.
4. The OH group in 2’ Carbon makes the RNA molecule prone to hydrolysis.
5. Some studies have also concluded that this chemical liability of RNA due to extra OH- the group has
led to DNA being the genetic storehouse as it lacks OH group in 2’Carbon making it more stable to
hold information.
6. RNA nucleotides carry the nitrogenous bases, Purines, and Pyrimidines. But in RNA in place of
Pyrimidine Thymine, Uracil is present which too forms hydrogen bonding with Adenine just as
Thymine does in DNA molecule.
7. RNA is a typical single-stranded biopolymer of ribonucleotides bonded with each other via a
phosphodiester bond.
8. An RNA strand is synthesized in the 5’ to 3’ direction from a locally single-stranded region of DNA.
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9. It has ribose sugars that are attached to four bases: Adenine, Guanine, Uracil, and Cytosine. Ribose
sugar has an extra OH- group in 2’ Carbon as compared to deoxyribose sugar in DNA.
10. This extra OH- group in RNA, has led them to be synthesized for short-term functions.
11. The three-dimensional structure of RNA is critical to its stability and function.
12. RNA being a single-stranded molecule can form a complex structure by allowing its ribose sugars
and bases to be modified on the action of cellular enzymes (that attach chemical groups), to perform
different functions.
13. They are even capable of folding on themselves and showing intramolecular hydrogen bonding
between complementary strands, making it a double-stranded molecule to exhibit specific function.
Composition of RNA
 RNA is a biopolymer of nucleotides bonded with each other via a phosphodiester bond.
 The nucleotide that makes up the RNA are also referred to as Ribose nucleotide due to the
presence of ribose sugar in their structure. Overall, RNA is composed of a ribose sugar,
phosphate, and nitrogenous base.
 Ribose sugar is a cyclical structure made up of five carbons and one oxygen atom. This sugar
contains two OH-groups at 2’ Carbon and 3’ Carbon.
 This ribose sugar is attached to a nitrogenous base via hydrogen bonding.
 There are four nitrogenous bases namely: Adenine (A), Guanine (G), Uracil (U), and Cytosine
(C).
 These nitrogenous bases pair complementarily with each other: G with C and A with U.
Types of RNA
Of many types of RNA, the three well known and most commonly discussed and found in almost all
organisms. These three types of RNA are:
1. mRNA (messenger RNA)
2. rRNA (ribosomal RNA)
3. tRNA (transfer RNA)
1. mRNA (messenger RNA)

 It is a single-stranded RNA molecule that is complementary to one of the strands of DNA.

 mRNA is the version of the genetic materials that leave the nucleus and move to the cytoplasm
where responsible proteins are synthesized.
 This RNA has utmost importance during protein synthesis, when the ribosome moves along this
mRNA, it reads the base sequences and uses the genetic code to translate them into specific
proteins.
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 These codes are in the form of triplet sequences of nitrogenous bases and are often referred to as
codons.
 As we now know that mRNA is responsible for transferring the genetic information into ribosomes
where by reading the base sequences on mRNA, the translation of proteins is made possible, thus
the name resembles its functions i.e., messenger RNA.
 We can even say mRNA is the molecule that uses genetic code present on a portion of DNA and
make proteins. If mRNA wouldn’t have existed then the information on DNA could never be used
by our body.
2. rRNA (ribosomal RNA)

 It is a single-stranded RNA molecule found in cells that forms the part of the protein-synthesizing
organelle, Ribosome.
 It is synthesized inside the nucleus particularly in the nucleolus where rRNA coding genes are
present. The synthesized rRNA can be of varying sizes, commonly distinguished as small and large.
 These newly synthesized rRNAs combine with ribosomal proteins and form smaller subunits and
larger subunits of ribosomes respectively.
 These rRNAs are vital in recognizing conserved regions of incoming mRNAs and tRNA thus
facilitating their binding and carrying out protein synthesis.
 Additionally, rRNA also has enzymatic activity (peptidyl transferase) and catalyzes the formation
of the peptide bond in between two aligned proteins/amino acids during protein synthesis.
 3. tRNA (transfer RNA)
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 It is a type of RNA molecule that helps to decode information present in mRNA sequences into
specific proteins.
 It is encoded by DNA in the cell nucleus and transcribed with the help of RNA polymerase ΙΙΙ.
 The structure of tRNA folds upon itself and creates an intra complementary base pairing which
gives raise to hydrogen-bonded stems and associated loops that contains nucleotides with modified
bases.
 The structure in two-dimensional resembles a cloverleaf having three loops and an open end. are
usually 75-90 ribonucleotides in length.
 Each of these loops consisting of arms has a distinct name and function. The three-loop consisting
arms are namely: DHU or D arm, which has recognition site for specific enzyme amino-acyl tRNA
synthetase; T arm that consists of ribosome recognition site and Anticodon arm that recognizes and
bind to mRNA present in the ribosome.
 The open end with no loop is the site for attachment of amino acid, via 3’ OH bonding with COOH-
group of the amino acid.
 In general, tRNA reads the code on the mRNA sequence in Ribosome and translates specific amino
acid, it does so along the length of the mRNA and gives out a polypeptide chain of amino acids
(proteins) in association with other important enzymes like aminoacyl tRNA synthetase and
peptidyl transferase.
Some other types of RNA
1. Ribozymes
 These types of RNAs refer to those RNAs that are capable of showing enzymatic activities.
 They were first discovered in introns of precursor ribosomal RNA of Tetrahymena thermophilus,
where it was found that these noncoding sequences were capable of excising themselves without
any protein or external source.
 These RNAs play vital roles in major reactions like RNA splicing, viral replication, and tRNA
biosynthesis.
 rRNAs also show enzymatic activities and thus can be termed as Ribozymes.
2. Antisense RNAs
 Antisense RNAs are those RNAs that contain sequences that are complementary to protein-
coding sequences of mRNA.
 These are single-stranded like mRNA but cannot code for proteins.
 However, they can interfere and inactivate their complementary mRNA sequences thus inhibiting
protein synthesis.
 This ability of antisense RNAs has led researchers to create artificial antisense RNAs that can
inhibit the protein synthesis of potential disease-causing organisms or of infected cells which then
end up killing unwanted cells.