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BOL 157:
BIOLOGICAL CHEMISTRY
Lecture 14:
Nucleic acids
Lecturer:
Christopher Larbie, PhD
Introduction
• Knowledge of how genes are expressed and how they
can be manipulated is becoming increasingly important
for understanding nearly every aspect of biochemistry.
• In this lecture we shall describe the chemical structures of
nucleic acids, and how we have come to know that DNA
as the carrier of genetic information, the structure of the
nucleotide bases, denaturation of DNA, and various forms
of DNA and RNA.
NUCLEOTIDES AND NUCLEIC ACIDS
• Nucleotides and their derivatives are biologically
ubiquitous substances that participate in nearly all
biochemical processes:
1. They form the monomeric units of nucleic acids and
thereby play central roles in both the storage and the
expression of genetic information.
2. Nucleoside triphosphates, most conspicuously ATP,
are the ―energy-rich‖ end products of the majority of
energy-releasing pathways and the substances whose
utilization drives most energy-requiring processes.
3. Most metabolic pathways are regulated, at least in part,
by the levels of nucleotides such as ATP and ADP.
• Moreover, certain nucleotides function as intracellular
signals that regulate the activities of numerous metabolic
processes.
4. Nucleotide derivatives, such as nicotinamide adenine
dinucleotide, flavin adenine dinucleotide, and
coenzyme A, are required participants in many
enzymatic reactions.
5. As components of the enzyme-like nucleic acids known
as ribozymes, nucleotides have important catalytic
activities themselves.
Nucleotides, Nucleosides, and Bases
• Nucleotides are phosphate esters of a five-carbon sugar
(which is therefore known as a pentose) in which a
nitrogenous base is covalently linked to C-1’ of the sugar
residue.
• In ribonucleotides, the monomeric units of RNA, the
pentose is D-ribose, whereas in deoxyribonucleotides
(or just deoxynucleotides), the monomeric units of DNA.
• The pentose is 2’-deoxy- D-ribose (note that the ―primed‖
numbers refer to the atoms of the ribose residue;
―unprimed‖ numbers refer to atoms of the nitrogenous
base)
•The phosphate group may be bonded to C5’ of the pentose to
form a 5’-nucleotide or to its C3’ to form a 3’-nucleotide
•If the phosphate group is absent, the compound is known as a
nucleoside. A 5’-nucleotide, for example, may therefore be
referred to as a nucleoside-5’-phosphate.
•In all naturally occurring nucleotides and nucleosides, the
bond linking the nitrogenous base to the pentose C1’ atom
(which is called a glycosidic bond) extends from the same side
of the ribose ring as does the C4’-C5’ bond (the β
configuration) rather than from the opposite side (the α
configuration).
•Note that nucleotide phosphate groups are doubly ionized at
physiological pH’s; that is, nucleotides are moderately strong
acids.
The Bases
• The nitrogenous bases are planar, aromatic, heterocyclic
molecules which, for the most part, are derivatives of
either purine or pyrimidine.
• The major purine components of nucleic acids are
adenine and guanine residues; the major pyrimidine
residues are those of cytosine, uracil (which occurs
mainly in RNA), and thymine (5-methyluracil, which
occurs mainly in DNA)
• The purines form glycosidic bonds to ribose via their N9
atoms, whereas pyrimidines do so through their N1
atoms.
Absorption of Ultraviolet Light
• Nucleic acids strongly absorb ultraviolet light of
wavelengths below about 300 nm, with an absorption
maximum at ~260 nm and a stronger one below 200 nm.
• This property is biologically important because of the
resultant induction of mutations, a natural result of
exposure to sunlight.
• In the laboratory the same property is useful in
identification and quantitative analysis of nucleotides.
Acid-base chemistry and tautomerism
• The ionized phosphate groups of the polymer ―backbone‖
give nucleic acid molecules a high negative charge.
• For this reason DNA in cells is usually associated with basic
proteins such as the histones or protamines (in
spermatozoa), with polycations of amines such as
spermidine (H3+NCH2CH2CH2CH2NH2+CH2CH2CH2NH3+),
or with alkaline earth cations such as Mg2+.
• If the pH of a solution containing double helical DNA is
either lowered to ~3 or raised to ~12, the two strands
unravel and can be separated.
• Over the entire range of pH the alternating sugar-
phosphate backbone of the polymeric chains remains
negatively charged.
• However, depending on the pH, the bases can be
protonated or deprotonated with a resultant breaking of
the hydrogen bonds that hold the pairs of bases together.
• Pyrimidines and purines, which contain the –NH2 group,
are weakly basic.
• The cationic protonated conjugate acid forms of cytidine,
adenosine, and guanosine have pKa values of 4.2, 3.5,
and 2.7, respectively.
• Similar values are observed for the 5'-nucleotides. In
these compounds it is not the –NH2 group that binds the
proton but an adjacent nitrogen atom in the ring.
• The bases have substantial aromatic character.
• This can be understood in terms of electronic interaction
with the adjacent oxygen
• Under basic conditions the proton on N-3 of uridine or
thymine or on N-1 of guanosine can dissociate with a pKa
of ~9.2
• These ―bases‖ are actually weak acids.
Reactions of Bases
• The purines and pyrimidines are relatively stable
compounds with considerable aromatic character.
• Nevertheless, they react with many different reagents
and, under some relatively mild conditions, can be
completely degraded to smaller molecules.
• The chemistry of these reactions is complex and is made
more so by the fact that a reaction at one site on the ring
may enhance the reactivity at other sites.
• The reactions of nucleic acids are largely the same as
those of the individual nucleosides or nucleotides.
• The rates of reaction are often influenced by the position
in the polynucleotide chain and by whether the nucleic
acid is single or double stranded.
• The reactions of nucleosides and nucleotides are best
understood in terms of the electronic properties of the
various positions in the bases.
• Most of the chemical reactions are nucleophilic addition or
displacement reactions.
• Positions 2, 4, and 6 of pyrimidine bases are deficient in
electrons and are therefore able to react with nucleophilic
reagents.
• The 6 position is especially reactive toward additions,
while the 2 position is the least reactive
• The corresponding electron-deficient positions in the
purine bases are 2, 6, and 8
• These positions, which are marked by asterisks, have
electrophilic character in all of the commonly occurring
pyrimidines and purines
The Chemical Structures of DNA and RNA
• The chemical structures of the nucleic acids were elucidated by
the early 1950s largely through the efforts of Phoebus Levene,
followed by the work of Alexander Todd.
• Nucleic acids are, with few exceptions, linear polymers of
nucleotides whose phosphate groups bridge the 3’ and 5’
positions of successive sugar residues.
• The phosphates of these polynucleotides, the
phosphodiester groups, are acidic, so that, at physiological
pH’s, nucleic acids are polyanions.
• Polynucleotides have directionality, that is, each has a 3’ end
(the end whose C3’ atom is not linked to a neighbouring
nucleotide) and a 5’ end (the end whose C5’ atom is not linked
to a neighbouring nucleotide).
DNA’s Base Composition Is Governed by
Chargaff’s Rules
• DNA has equal numbers of adenine and thymine residues
(A = T) and equal numbers of guanine and cytosine
residues (G = C)
• These relationships, known as Chargaff’s rules.
• Chargaff also found that the base composition of DNA
from a given organism is characteristic of that organism,
that is, it is independent of the tissue from which the DNA
is taken as well as the organism’s age, its nutritional state,
or any other environmental factor.
•.
• DNA’s base composition varies widely among different
organisms
• It ranges from ~25% to 75% G = C in different species of
bacteria. It is, however, more or less constant among
related species; for example, in mammals G = C ranges
from 39% to 46%.
• RNA, which usually occurs as single-stranded molecules,
has no apparent constraints on its base composition.
• However, double-stranded RNA, which comprises the
genetic material of certain viruses, also obeys Chargaff’s
rules (here A base pairs with U in the same way it does
with T in DNA).
Base Pairs, Triplets, and Quartets
• The purine and pyrimidine bases are the ―side chains‖ of
the nucleic acids.
• The polar groups that are present in the bases can form
hydrogen bonds to other nucleic acid chains, e.g., in the
base pairs of the DNA double helix, and also to proteins.
• The number of both electron donor groups and proton
donors available for hydrogen bonding is large and more
than one mode of base pairing is possible.
• While X-ray diffraction studies indicate that it is these
pairs that usually exist in DNA, other possibilities must be
considered.
• For example, Hoogsteen proposed an alternative A-T
pairing using the 6-NH2 and N-7 of adenine.
• Here the distance spanned by the base pair, between the
C-1' sugar carbons, is 0.88 nm, less than the 1.08 nm of
the Watson–Crick pairs.
• Duplexes of certain substituted poly (A) and poly (U)
chains contain only Hoogsteen base pairs and numerous
X-ray structure determinations have established that
Hoogsteen pairs do occur in true nucleic acids.
Strengths of base pairs
• How strong are the bonds between pairs of bases in
DNA?
• The question is hard to answer because of the strong
interaction of the molecules with polar solvents through
hydrogen bonding and hydrophobic effects.
• Some insight has come from studies of the association of
bases in nonpolar solvents.
• The small energies summed over the many base pairs
present in the DNA molecule help provide stability to the
structure.
Stacking of bases
• The purines and pyrimidines of nucleic acids, as well as
many other compounds with flat ring structures and
containing both polar and nonpolar regions, are sparingly
soluble in either water or organic solvents.
• Molecules of these substances prefer neither type of
solvent but adhere tightly to each other in solid crystals.
• Both experimental measurements and theoretical
computations suggest that hydrogen bonding is the
predominant force in the pairing of bases in a vacuum or
in nonpolar solvents.
• However, in water stacking becomes important.
• In a fully extended polynucleotide chain consecutive
bases are 0.7 nm apart, twice the van der Waals
thickness of a pyrimidine or purine ring, but in doublehelical DNA the distance between consecutive base pairs
is only 0.34 nm.
• The molar extinction coefficient of a solution of double-
helical DNA or RNA is always less by up to 20–30% than
that predicted from the spectra of the individual
nucleosides.
Modification of Nucleic Acid Bases
• Some DNAs contain bases that are chemical derivatives
of the standard set.
• For example, dA and dC in the DNAs of many organisms
are partially replaced by N6-methyl-dA and 5-methyl-dC,
respectively.
• The altered bases are generated by the sequence-
specific enzymatic modification of normal DNA.
• The modified DNAs obey Chargaff’s rules if the
derivatized bases are taken as equivalent to their parent
bases.
• Likewise, many bases in RNAs and, in particular, those in
transfer RNAs (tRNAs) are derivatized
Susceptibility of RNA but Not DNA to BaseCatalysed Hydrolysis
• RNA is highly susceptible to base-catalysed as to yield a
mixture of 2’ and 3’ nucleotides.
• In contrast, DNA, which lacks 2’-OH groups, is resistant to
base-catalysed hydrolysis and is therefore much more
chemically stable than RNA.
• This is probably why DNA rather than RNA evolved to be
the cellular genetic archive.
Levels of organization of structure of DNA
• Like proteins, DNA has various levels of organisation of its
structure such as Primary, secondary, tertiary and
quaternary structures.
Primary structure
• This refers to a single DNA chain of a long threadlike
molecule, composed of numerous DNA.
• The primary structure is the backbone of the DNA
structure in which the deoxyriboses of successive
nucleotides are linked by covalent phosphodiester bridges
between the 3’ and 5’ hydroxyl groups of adjacent sugar
molecules.
Secondary structure
• This refers to the steric relationship of bases which are
close to each other in the linear arrangement of
nucleotides e.g. the double helical structure.
• Here, the bases of the two strands lie in the centre of the
molecule, with the sugar-phosphate backbone on the
outside.
• An important feature is that the bases in the two strands
are complementary, but not identical.
• The complementarity is attributed to the appropriate base
pairings of the strands as described by the Chargaff’s
rule.
• The H-bonding between the bases is weak, but
collectively, the H-bonds in the double helix give rise to a
stable molecule.
• Stability is also achieved by the forces arising from the
partial overlap of the hydrophobic bases of successive
nucleotides along the chain (base stacking described
above).
Tertiary structure
• This refers to the steric relationship of segments of the
polynucleotide that are apart in linear relationship.
• A circular double-standed DNA without folding is called a
Relaxed DNA and this present the most simple and most
stable tertiary structure of DNA.
• To fit into cells, chromosomal DNA has to be compactly
folded. Examples are relaxed, looped, superhelical
conformations and their combinations.
Denaturation of DNA
• When a solution of duplex DNA is heated above a
characteristic temperature, its native structure collapses
and its two complementary strands separate and assume
a flexible and rapidly fluctuating conformational state
known as a random coil.
• This denaturation process is accompanied by a
qualitative change in the DNA’s physical properties.
• For instance, the characteristic high viscosity of native
DNA solutions, which arises from the resistance to
deformation of its rigid and rod-like duplex molecules,
drastically decreases when the duplex DNA decomposes
(denatures) to two relatively freely jointed single strands.
• The most convenient way of monitoring the amount of
nucleic acid present is by its ultraviolet (UV) absorbance
spectrum. When DNA denatures, its UV absorbance
increases by ~40% at all wavelengths.
• This phenomenon is known as the hyperchromic effect, and
results from the disruption of the electronic interactions among
nearby bases.
• DNA’s hyperchromic shift, as monitored at a particular
wavelength (usually 260 nm), occurs over a narrow
temperature range.
• This indicates that the collapse of one part of the duplex DNA’s
structure destabilizes the remainder, a phenomenon known as
a cooperative process.
• The denaturation of DNA may be described as the melting of a
one-dimensional solid, represented by a melting curve and
the temperature at its midpoint is known as the melting
temperature, Tm.
• The stability of the DNA double helix, and hence its Tm,
depends on several factors, including the nature of the
solvent, the identities and concentrations of the ions in
solution, and the pH.
• For example, duplex DNA denatures (its Tm decreases)
under alkaline conditions that cause some of the bases to
ionize and thereby disrupt their base pairing interactions.
• The Tm increases linearly with the mole fraction of G - C
base pairs, which indicates that triply hydrogen bonded G
- C base pairs are more stable than doubly hydrogen
bonded A - T base pairs.
Types of DNA Structure
• Three major forms of DNA are double stranded and
connected by interactions between complementary base
pairs. These are terms A-form, B-form, and Z-form DNA.
B-form DNA
• The information from the base composition of DNA, the
knowledge of dinucleotide structure, and the insight that
the X-ray crystallography suggested a helical periodicity.
• They proposed two strands of DNA, each in a right-hand
helix, wound around the same axis. The two strands are
held together by H-bonding between the bases (in anticonformation).
• The two strands are not in a simple side-by-side
arrangement, which would be called a paranemic joint.
• Rather the two strands are coiled around the same helical
axis and are intertwined with themselves (which is
referred to as a plectonemic coil).
• One consequence of this intertwining is that the two
strands cannot be separated without the DNA rotating,
one turn of the DNA for every "untwisting" of the two
strands
Dimensions of B-form (the most common) of DNA
• 0.34 nm between bp, 3.4 nm per turn, about 10 bp per
turn
• 1.9 nm (about 2.0 nm or 20 A) in diameter
Major and minor groove
• The major groove is wider than the minor groove in DNA,
and many sequence specific proteins interact in the major
groove.
• The N7 and C6 groups of purines and the C4 and C5
groups of pyrimidines face into the major groove, thus
they can make specific contacts with amino acids in DNAbinding proteins.
• Thus specific amino acids serve as H-bond donors and
acceptors to form H-bonds with specific nucleotides in the
DNA.
• H-bond donors and acceptors are also in the minor
groove, and indeed some proteins bind specifically in the
minor groove.
• Base pairs stack, with some rotation between them.
A-DNA and Z-DNA
• A-form DNA has thicker right-handed duplex with a
shorter distance between the base pairs for RNA-DNA
duplexes and RNA-RNA duplexes.
• The Z-DNA is formed by stretches of alternating purines
and pyrimidines, e.g. GCGCGC, especially in negatively
supercoiled DNA.
• A small amount of the DNA in a cell exists in the Z form.
• It has been enticing to propose that this different structure
is involved in some way in regulation of some cellular
function. This include transcription or regulation, but
conclusive evidence for or against this proposal is not
available yet.
Differences between A-form and B-form
nucleic acid
• The major difference between A-form and B-form nucleic
acid is in the conformation of the deoxyribose sugar ring.
• It is in the C2' endo-conformation for B-form, whereas it is
in the C3' endo-conformation in A-form.
• If you consider the plane defined by the C4'-O-C1' atoms
of the deoxyribose, in the C2' endoconformation, the C2'
atom is above the plane, whereas the C3' atom is above
the plane in the C3' endoconformation
• The latter conformation brings the 5' and 3' hydroxyls
(both esterified to the phosphates linking to the next
nucleotides) closer together than is seen in the C2'
endoconfromation.
• Thus the distance between adjacent nucleotides is
reduced by about 1 A in A-form relative to B-form nucleic
acid.
• A second major difference between A-form and B-form
nucleic acid is the placement of base-pairs within the
duplex. In B-form, the base-pairs are almost centred over
the helical axis, but in A-form, they are displaced away
from the central axis and closer to the major groove. The
result is a ribbon-like helix with a more open cylindrical
core in A-form.
DNA as storage of Genetic information
• The DNA is a large molecule with infinite variety so can
store so much information.
• It is the repository of all the information required by the
cell. However, the information for the synthesis of proteins
accounts for most of the information stored in the DNA.
• It is the genes which encode the information that
determines the structure of proteins.
• In turn, the structure of proteins dictates the activity of the
protein which also determines the physiological role of the
cell.
• Another important characteristic of DNA is its capability to
undergo faithful replication.
• This ensures that the information contained in it are
transmitted from one generation to the other by
reproduction of organisms or by cell division or both.
• Another important feature is that DNA is a stable molecule
resisting hydrolysis and mutations.
RIBONUCLEIC ACID (RNA)
• Ribonucleic acid (RNA) is a ubiquitous family of large
biological molecules that perform multiple vital roles in
the coding, decoding, regulation, and
expression of genes.
• Together with DNA, RNA comprises the nucleic acids,
which, along with proteins, constitute the three
major macromolecules essential for all known forms
of life.
• Like DNA, RNA is assembled as a chain of nucleotides,
but is usually single-stranded.
• Some RNA molecules play an active role within cells by
catalysing biological reactions, controlling gene
expression, or sensing and communicating responses to
cellular signals.
• One of these active processes is protein synthesis, a
universal function whereby mRNA molecules direct the
assembly of proteins on ribosomes.
• This process uses transfer RNA (tRNA) molecules to
deliver amino acids to the ribosome, where ribosomal
RNA (rRNA) links amino acids together to form proteins.
• The chemical structure of RNA is very similar to that
of DNA, but differs in three main ways:
1. Unlike double-stranded DNA, RNA is a single-stranded
molecule in many of its biological roles and has a much
shorter chain of nucleotides. However, RNA can, by
complementary base pairing, form intra-strand double
helixes, as in tRNA.
2. While DNA contains deoxyribose, RNA
contains ribose (in deoxyribose there is no hydroxyl group
attached to the pentose ring in the 2' position). These
hydroxyl groups make RNA less stable than DNA because
it is more prone to hydrolysis.
3. The complementary base to adenine is not thymine, as it
is in DNA, but rather uracil, which is an unmethylated form
of thymine
• Like DNA, most biologically active RNAs,
including mRNA, tRNA, rRNA, snRNAs, and other noncoding RNAs. They contain self-complementary
sequences that allow parts of the RNA to fold and pair
with itself to form double helices
• Analysis of these RNAs has revealed that they are highly
structured.
• Unlike DNA, their structures do not consist of long double
helices but rather collections of short helices packed
together into structures similar to proteins.
• In this fashion, RNAs can achieve chemical catalysis, like
enzymes. For instance, determination of the structure of
the ribosome—an enzyme that catalyses peptide bond
formation—revealed that its active site is composed
entirely of RNA.
Messenger RNA (mRNA)
• Messenger RNA (mRNA) is a large family
of RNA molecules that convey genetic
information from DNA to the ribosome, where they specify
the amino acid sequence of the protein products of gene
expression.
• Following transcription of primary transcript mRNA (pre-
mRNA) by RNA polymerase, processed, mature mRNA
is translated into a polymer of amino acids: a protein.
• As in DNA, mRNA genetic information is encoded in the
sequence of nucleotides, which are arranged
into codons consisting of three bases each.
• Each codon encodes for a specific amino acid, except
the stop codons, which terminate protein synthesis.
• This process of translation of codons into amino acids
requires two other types of RNA:
• Transfer RNA (tRNA), that mediates recognition of the
codon and provides the corresponding amino acid,
and ribosomal RNA (rRNA), that is the central
component of the ribosome's protein-manufacturing
machinery.
Transfer RNA (tRNA)
• A Transfer RNA (abbreviated tRNA and archaically
referred to as sRNA abbreviating soluble RNA) is an
adaptor molecule composed of RNA, typically 73 to
94 nucleotides in length, that serves as the physical link
between the nucleotide sequence of nucleic
acids (DNA and RNA) and the amino acid sequence of
proteins.
• It does this by carrying an amino acid to the protein
synthetic machinery of a cell (ribosome) as directed by a
three-nucleotide sequence (codon) in a messenger
RNA (mRNA).
• As such, tRNAs are a necessary component of protein
translation, the biological synthesis of
new proteins according to the genetic code.
• The specific nucleotide sequence of an mRNA specifies
which amino acids are incorporated into the protein
product of the gene from which the mRNA is transcribed.
• The role of tRNA is to specify which sequence from the
genetic code corresponds to which amino acid.
• One end of the tRNA matches the genetic code in a three-
nucleotide sequence called the anticodon.
• The anticodon forms three base pairs with a codon in
mRNA during protein biosynthesis.
• The mRNA encodes a protein as a series of contiguous
codons, each of which is recognized by a particular tRNA.
• On the other end of the tRNA is a covalent attachment to
the amino acid that corresponds to the anticodon
sequence.
• Each type of tRNA molecule can be attached to only one
type of amino acid, so each organism has many types of
tRNA .
• In fact, because the genetic code contains multiple
codons that specify the same amino acid, there are many
tRNA molecules bearing different anticodons which also
carry the same amino acid.
• The covalent attachment to the tRNA 3’ end is catalysed
by enzymes called aminoacyl-tRNA synthetases.
• During protein synthesis, tRNAs with attached amino
acids are delivered to the ribosome by proteins
called elongation factors (EF-Tu in bacteria, eEF-1 in
eukaryotes).
• These aid in decoding the mRNA codon sequence.
• If the tRNA's anticodon matches the mRNA, another tRNA
already bound to the ribosome transfers the growing
polypeptide chain from its 3’ end to the amino acid
attached to the 3’ end of the newly delivered tRNA, a
reaction catalysed by the ribosome.
Ribosomal RNA
• Ribosomal ribonucleic acid (rRNA) is the RNA component
of the ribosome.
• It is essential for protein synthesis in all living organisms.
It constitutes the predominant material within the
ribosome, which is approximately 60% rRNA and 40%
protein by weight.
• Ribosomes contain two major rRNAs and 50 or
more proteins.
• The LSU and SSU rRNAs are found within the large and
small ribosomal subunits, respectively.
• The LSU rRNA acts as a ribozyme, catalysing peptide
bond formation.
• rRNA sequences are widely used for working out
evolutionary relationships among organisms, since they
are of ancient origin and are found in all known forms of
life.
Small Nuclear RNA
• Small nuclear ribonucleic acid (snRNA), also commonly
referred to as U-RNA, is a class of small RNA molecules
that are found within the nucleus of eukaryotic cells.
• The length of an average snRNA is approximately 150
nucleotides.
• They are transcribed by either RNA polymerase II or RNA
polymerase III, and studies have shown that their primary
function is in the processing of pre-mRNA (hnRNA) in the
nucleus.
• They have also been shown to aid in the regulation
of transcription factors (7SK RNA) or RNA polymerase II
(B2 RNA), and maintaining the telomeres.
• snRNA are always associated with a set of specific
proteins, and the complexes are referred to as small
nuclear ribonucleoproteins (snRNP) often pronounced
"snurps‖.
• Each snRNP particle is composed of several Sm proteins,
the snRNA component, and snRNP specific proteins.
• The most common snRNA components of these
complexes are known, respectively, as: U1 snRNA, U2
snRNA, U4 snRNA, U5 snRNA, and U6 snRNA.
• Their nomenclature derives from their high uridine
content.
• A large group of snRNAs are known as small nucleolar
RNAs (snoRNAs). These are small RNA molecules that
play an essential role in RNA biogenesis and guide
chemical modifications of ribosomal RNAs (rRNAs) and
other RNA genes (tRNA and snRNAs).
• They are located in the nucleolus and the Cajal
bodies of eukaryotic cells (the major sites of RNA
synthesis), where they are called scaRNAs (small Cajal
body-specific RNAs).
Non-Coding RNA
• A non-coding RNA (ncRNA) is a functional RNA molecule
that is not translated into a protein.
• Less-frequently used synonyms are non-protein-coding
RNA (npcRNA), non-messenger RNA (nmRNA) and
functional RNA (fRNA).
• The term small RNA (sRNA) is often used for short
bacterial ncRNAs.
• The DNA sequence from which a non-coding RNA is
transcribed is often called an RNA gene.
• Non-coding RNA genes include highly abundant and
functionally important RNAs such as transfer RNA (tRNA)
and ribosomal RNA (rRNA), as well as RNAs such
as snoRNAs, microRNAs, siRNAs, snRNAs, exRNAs,
and piRNAs and the long ncRNAs that include examples
such as Xist and HOTAIR.
• The number of ncRNAs encoded within the human
genome is unknown, however, recent transcriptomic and
bioinformatic studies suggest the existence of thousands
of ncRNAs.
• Since many of the newly identified ncRNAs have not been
validated for their function, it is possible that many are
non-functional.
Other nuclei acids and analogs
• When adenine is deaminated, hypoxanthine is formed,
and the deamination of guanine gives xanthine.
• Both are enzymatically oxidized to give uric acid. Uric acid
can form sodium salts which can deposit in soft tissues,
giving rise to inflammation of affected tissues as occurs in
gout.
• Others have pharmacological activities including caffeine,
theobromine and theophylline.
• Nuclei acid analogs are compounds which are have
similar structures to the pyrimidines or purines or their
nucleosides and can be exploited as drugs particularly as
anticancer.
• Example, 5-flurouracil, 6-thioguanine, 6-mercaptopurine
and 3’-azido-2’,3’-dideoxythymine or azidodideoxythymine
(AZT).
• These analogs are incorporated in nuclei acids of
proliferating cancer cells, inhibiting growth.