The Molecular Basis of Inheritance

Nucleic Acids
 The amino acid sequence of a polypeptide is
programmed by a unit of inheritance called a
gene
 Genes are made of DNA, a nucleic acid made
of monomers called nucleotides.
The Roles of Nucleic Acids
 There are two types of nucleic acids
• Deoxyribonucleic acid (DNA)
• Ribonucleic acid (RNA)
 DNA provides directions for its own
replication
 DNA directs synthesis of messenger RNA
(mRNA) and, through mRNA, controls
protein synthesis
 Protein synthesis occurs on ribosomes
 DNA

1 Synthesis of
mRNA
mRNA

NUCLEUS
CYTOPLASM

mRNA
2 Movement of
mRNA into Ribosome
cytoplasm

3 Synthesis
of protein

Amino
Polypeptide acids
The Components of Nucleic Acids

 Nucleic acids are polymers called

polynucleotides
 Each polynucleotide is made of monomers
called nucleotides
 Each nucleotide consists of a nitrogenous
base, a pentose sugar, and one or more
phosphate groups
 The portion of a nucleotide without the
phosphate group is called a nucleoside
 Sugar-phosphate backbone
5 end Nitrogenous bases
Pyrimidines
5C

3C

Nucleoside

Nitrogenous
base Cytosine (C) Thymine (T, in DNA) Uracil (U, in RNA)

5C Purines

1C
Phosphate 3C
group Sugar
5C
(pentose)
Adenine (A) Guanine (G)
3C (b) Nucleotide

Sugars
3 end
(a) Polynucleotide, or nucleic acid

Deoxyribose (in DNA) Ribose (in RNA)

(c) Nucleoside components

 Nucleoside = nitrogenous base + sugar
 There are two families of nitrogenous bases
• Pyrimidines (cytosine, thymine, and uracil)
have a single six-membered ring
• Purines (adenine and guanine) have a six-
membered ring fused to a five-membered ring
 In DNA, the sugar is deoxyribose; in RNA, the
sugar is ribose
 Nucleotide = nucleoside + phosphate group
 Nucleotide Polymers
 Nucleotide polymers are linked together to build
a polynucleotide
 Adjacent nucleotides are joined by covalent
bonds that form between the —OH group on the
3 carbon of one nucleotide and the phosphate
on the 5 carbon on the next
 These links create a backbone of sugar-
phosphate units with nitrogenous bases as
appendages
 The sequence of bases along a DNA or mRNA
polymer is unique for each gene
The Structures of DNA and RNA Molecules

 RNA molecules usually exist as single

polypeptide chains
 DNA molecules have two polynucleotides
spiraling around an imaginary axis, forming a
double helix
 In the DNA double helix, the two backbones
run in opposite 5→ 3 directions from each
other, an arrangement referred to as
antiparallel
 One DNA molecule includes many genes
 The nitrogenous bases in DNA pair up and form
hydrogen bonds: adenine (A) always with
thymine (T), and guanine (G) always with
cytosine (C)
 Called complementary base pairing
 Complementary pairing can also occur between
two RNA molecules or between parts of the same
molecule
 In RNA, thymine is replaced by uracil (U) so A
and U pair
5 3 Sugar-phosphate
backbones
Hydrogen bonds

Base pair joined

by hydrogen
bonding

3 5 Base pair joined

by hydrogen bonding
(a) DNA (b) Transfer RNA
 Proteins

 Proteins account for more than 50% of the dry

mass of most cells
 Protein functions include structural support,
storage, transport, cellular communications,
movement, and defense against foreign
substances
Enzymatic proteins Defensive proteins
Function: Selective acceleration of chemical reactions Function: Protection against disease
Example: Digestive enzymes catalyze the hydrolysis Example: Antibodies inactivate and help destroy
of bonds in food molecules. viruses and bacteria.

Antibodies

Enzyme Virus Bacterium

Storage proteins Transport proteins

Function: Storage of amino acids
Examples: Casein, the protein of milk, is the major
source of amino acids for baby mammals. Plants have
storage proteins in their seeds. Ovalbumin is the
protein of egg white, used as an amino acid source
for the developing embryo.
Function: Transport of substances
Examples: Hemoglobin, the iron-containing protein of
vertebrate blood, transports oxygen from the lungs to
other parts of the body. Other proteins transport
molecules across cell membranes.
Transport
protein

Ovalbumin Amino acids

for embryo Cell membrane
Hormonal proteins
Function: Coordination of an organism’s activities
Example: Insulin, a hormone secreted by the
pancreas, causes other tissues to take up glucose,
thus regulating blood sugar concentration
Receptor proteins
Function: Response of cell to chemical stimuli
Example: Receptors built into the membrane of a
nerve cell detect signaling molecules released by
other nerve cells.

Receptor
Signaling protein
Insulin
High secreted Normal molecules
blood sugar blood sugar

Contractile and motor proteins Structural proteins

Function: Movement
Examples: Motor proteins are responsible for the
undulations of cilia and flagella. Actin and myosin
proteins are responsible for the contraction of
muscles.
Function: Support
Examples: Keratin is the protein of hair, horns,
feathers, and other skin appendages. Insects and
spiders use silk fibers to make their cocoons and webs,
respectively. Collagen and elastin proteins provide a
fibrous framework in animal connective tissues.

Actin Myosin
Collagen

Muscle tissue Connective

100 m tissue 60 m
 Enzymes are a type of protein that acts as a
catalyst to speed up chemical reactions
 Enzymes can perform their functions
repeatedly, functioning as workhorses that
carry out the processes of life
Polypeptides
 Polypeptides are unbranched polymers built
from the same set of 20 amino acids
 A protein is a biologically functional molecule
that consists of one or more polypeptides
Amino Acid Monomers
 Amino acids are organic molecules with
carboxyl and amino groups
 Amino acids differ in their properties due to
differing side chains, called R groups
Side chain (R group)

 carbon

Amino Carboxyl
group group
Nonpolar side chains; hydrophobic
Side chain
(R group)

Glycine Alanine Valine Leucine Isoleucine

(Gly or G) (Ala or A) (Val or V) (Leu or L) (Ile or I)

Methionine Phenylalanine Tryptophan Proline

(Met or M) (Phe or F) (Trp or W) (Pro or P)

Polar side chains; hydrophilic

Serine Threonine Cysteine Tyrosine Asparagine Glutamine

(Ser or S) (Thr or T) (Cys or C) (Tyr or Y) (Asn or N) (Gln or Q)

Electrically charged side chains; hydrophilic Basic (positively charged)

Acidic (negatively charged)

Aspartic acid Glutamic acid Lysine Arginine Histidine

(Asp or D) (Glu or E) (Lys or K) (Arg or R) (His or H)
 Amino Acid Polymers
 Amino acids are linked by peptide bonds
 A polypeptide is a polymer of amino acids
 Polypeptides range in length from a few to
more than a thousand monomers
 Each polypeptide has a unique linear
sequence of amino acids, with a carboxyl end
(C-terminus) and an amino end (N-
terminus)

© 2011 Pearson Education, Inc.

Figure 5.17

Peptide bond

New peptide
bond forming

Side
chains

Back-
bone

Amino end Peptide Carboxyl end

(N-terminus) bond (C-terminus)
 Protein Structure and Function
 A functional protein consists of one or more
polypeptides precisely twisted, folded, and
coiled into a unique shape
 The sequence of amino acids determines a
protein’s three-dimensional structure
 A protein’s structure determines its function
Antibody protein Protein from flu virus
 Four Levels of Protein Structure

 The primary structure of a protein is its unique

sequence of amino acids
 Secondary structure, found in most proteins,
consists of coils and folds in the polypeptide
chain
 Tertiary structure is determined by interactions
among various side chains (R groups)
 Quaternary structure results when a protein
consists of multiple polypeptide chains

© 2011 Pearson Education, Inc.

Figure 5.20a
Primary structure

Amino
acids

Amino end

Primary structure of transthyretin

Carboxyl end
 Primary structure, the sequence of amino
acids in a protein, is like the order of letters
in a long word
 Primary structure is determined by inherited
genetic information
 Secondary Tertiary Quaternary
structure structure structure

 helix

Hydrogen bond
 pleated sheet
 strand
Transthyretin
Hydrogen Transthyretin protein
bond polypeptide
  The coils and folds of secondary structure
result from hydrogen bonds between repeating
constituents of the polypeptide backbone
 Typical secondary structures are a coil called
an  helix and a folded structure called a 
pleated sheet

© 2011 Pearson Education, Inc.

Figure 5.20c
Secondary structure

 helix

Hydrogen bond
 pleated sheet

 strand, shown as a flat

arrow pointing toward
the carboxyl end

Hydrogen bond
  Tertiary structure is determined by
interactions between R groups, rather than
interactions between backbone constituents
 These interactions between R groups include
hydrogen bonds, ionic bonds, hydrophobic
interactions, and van der Waals interactions
 Strong covalent bonds called disulfide
bridges may reinforce the protein’s structure

© 2011 Pearson Education, Inc.

Figure 5.20f

Hydrogen
bond
Hydrophobic
interactions and
van der Waals
interactions
Disulfide
bridge
Ionic bond

Polypeptide
backbone
  Quaternary structure results when two or
more polypeptide chains form one
macromolecule
 Collagen is a fibrous protein consisting of three
polypeptides coiled like a rope
 Hemoglobin is a globular protein consisting of
four polypeptides: two alpha and two beta
chains

© 2011 Pearson Education, Inc.

 Heme
Iron
 subunit

 subunit

 subunit

 subunit

Hemoglobin
What is DNA?

 A DNA molecule
consists of two G

A
C

strands of 1 nm
T A

nucleotide C G
G C
3.4 nm

monomers running C
A

G
T

in opposite
T A

directions and T A

A T
coiled into a double A T

helix G C
0.34 nm
A T

(a) Key features of DNA structure (c) Space-filling model

 1962: Nobel Prize in Physiology and Medicine

Watson, J.D. and F.H. Crick, “Molecular Structure of Nucleic

Acids: A Structure for Deoxynucleic Acids”. Nature 171 (1953),
p. 738.

James D. Francis H. Maurice H. F.

Watson Crick Wilkins
What about?
Rosalind Franklin
Fame and Glory
 Rosalind Franklin
• Discovered the basic structure of DNA by x-ray
crystallography

 Erwin Chargaff
• Discovered the relationships between DNA bases

 James Watson and Francis Crick

• Built the first accurate model of a DNA molecule
What are the Structures of DNA?
 The Structures of DNA
 DNA is composed of four
nucleotides, each containing:
adenine, cytosine, thymine, or
guanine.
 The amounts of A = T, G = C, or
purines = pyrimidines
[Chargaff’s Rule].
 DNA is a double-stranded helix
with antiparallel strands [Watson
and Crick].
 Nucleotides in each strand are
linked by 5’-3’ phosphodiester
bonds
 Bases on opposite strands are
linked by hydrogen bonding: A
with T, and G with C.
The Four DNA Nucleotides
DNA Structure
 Patterns of Base Pairing
 The order of bases (DNA sequence) varies
among species and among individuals
• Each species has characteristic DNA sequences

 DNA sequence
• The order of nucleotide bases in a strand of DNA
DNA Replication: The Double Helix
DNA Replication
 DNA replication
• Duplication of a cell’s DNA before cell division
 Each strand of the double helix serves as a
template for synthesis of a new, complementary
strand of DNA
 DNA replication results in two double-stranded
DNA molecules identical to the parent
DNA Replication
 DNA replication
 The parent molecule unwinds, and two new
daughter strands are built based on base-pairing
rules

T
A T A T A A T A T A T
C G C G C G C G C G C G
T A T A T A T A T A T A
A T A T A T A T A T A T
G C G C G C C G C G C
G

(a) The parent molecule has two
complementary strands of DNA.
Each base is paired by hydrogen
bonding with its specific partner,
A with T and G with C.
(b) The first step in replication is
separation of the two DNA
strands.
(c) Each parental strand now
serves as a template that
determines the order of
nucleotides along a new,
complementary strand.
(d) The nucleotides are connected
to form the sugar-phosphate
backbones of the new strands.
Each “daughter” DNA
molecule consists of one parental
strand and one new strand.
DNA Replication is “Semi-conservative”

 Each 2-strand
daughter molecule
is only half new
 One original
strand was used
as a template to
make the new
strand
 DNA Replication
 The copying of DNA is remarkable in its speed and
accuracy
 Involves unwinding the double helix and synthesizing two
new strands.
 More than a dozen enzymes and other proteins participate
in DNA replication
 The replication of a DNA molecule begins at special sites
called origins of replication, where the two strands are
separated
Mechanism of DNA Replication
 DNA replication is catalyzed by DNA polymerase which needs an
RNA primer
 RNA primase synthesizes primer on DNA strand
 DNA polymerase adds nucleotides to the 3’ end of the growing
strand
 Mechanism of DNA Replication

 Nucleotides are
added by
complementary
base pairing with the
template strand
 The substrates,
deoxyribonucleoside
triphosphates, are
hydrolyzed as
added, releasing
energy for DNA
synthesis.
The Mechanism of DNA Replication
 DNA synthesis on the leading strand is continuous.
 The lagging strand grows the same general direction as the leading
strand (in the same direction as the Replication Fork). However,
DNA is made in the 5’-to-3’ direction
 Therefore, DNA synthesis on the lagging strand is discontinuous
 DNA is added as short fragments (Okasaki fragments) that are
subsequently ligated together
DNA polymerase I degrades the
RNA primer and replaces it with
DNA
 The Mechanism of DNA Replication
 Many proteins assist in DNA
replication
 DNA helicases unwind the double
helix, the template strands are
stabilized by other proteins
 Single-stranded DNA binding proteins
make the template available
 RNA primase catalyzes the
synthesis of short RNA primers, to
which nucleotides are added.
 DNA polymerase III extends the
strand in the 5’-to-3’ direction
 DNA polymerase I degrades the
RNA primer and replaces it with DNA
 DNA ligase joins the DNA fragments
into a continuous daughter strand
 Enzymes in DNA replication

Helicase unwinds Binding proteins Primase adds

parental double helix stabilize separate short primer
strands to template strand

DNA polymerase III DNA polymerase I Ligase joins Okazaki

binds nucleotides (Exonuclease) removes fragments and seals
to form new strands RNA primer and inserts other nicks in sugar-
the correct bases phosphate backbone
 Replication
3’
3’ 5’
5’
3’

5’ 3’
5’

Helicase protein binds to DNA sequences called

origins and unwinds DNA strands.
Binding proteins prevent single strands from rewinding.
Primase protein makes a short segment of RNA
complementary to the DNA, a primer.
Replication
Overall direction 3’
of replication
3’ 5’
5’

3’

5’ 3’
5’

DNA polymerase enzyme adds DNA nucleotides

to the RNA primer.
Replication
Overall direction
3’
of replication
3’ 5’

5’
3’

5’ 3’
5’

DNA polymerase enzyme adds DNA nucleotides

to the RNA primer.
DNA polymerase proofreads bases added and
replaces incorrect nucleotides.
Replication
Overall direction
3’
of replication
3’ 5’

5’
3’

5’ 3’
5’

Leading strand synthesis continues in a

5’ to 3’ direction.
Replication
Overall direction
3’
of replication
3’ 5’

5’
Okazaki fragment
3’

5’ 3’ 5’ 3’
5’

Leading strand synthesis continues in a

5’ to 3’ direction.
Discontinuous synthesis produces 5’ to 3’ DNA
segments called Okazaki fragments.
Replication
Overall direction
3’
of replication
3’ 5’

5’
Okazaki fragment
3’

5’ 3’ 5’ 3’
5’

Leading strand synthesis continues in a

5’ to 3’ direction.
Discontinuous synthesis produces 5’ to 3’ DNA
segments called Okazaki fragments.
 Replication

3’
3’ 5’

5’
3’
5’ 3’ 5’ 3’5’ 3’
5’

Leading strand synthesis continues in a

5’ to 3’ direction.
Discontinuous synthesis produces 5’ to 3’ DNA
segments called Okazaki fragments.
 Replication

3’
3’ 5’

5’
3’
5’ 3’5’ 3’5’ 3’
5’

Leading strand synthesis continues in a

5’ to 3’ direction.
Discontinuous synthesis produces 5’ to 3’ DNA
segments called Okazaki fragments.
 Replication

3’
3’ 5’

5’
3’
5’ 3’5’ 3’5’ 3’
5’

Exonuclease activity of DNA polymerase I

removes RNA primers.
 Replication

3’
3’

5’
3’
5’ 3’5’ 3’
5’

Polymerase activity of DNA polymerase I fills the gaps.

Ligase forms bonds between sugar-phosphate backbone.
Replication Fork Overview
Proofreading
 DNA must be faithfully replicated…but
mistakes occur
• DNA polymerase (DNA pol) inserts the wrong
nucleotide base in 1/10,000 bases
• DNA pol has a proofreading capability and can
correct errors
• Mismatch repair: ‘wrong’ inserted base can be
removed
• Excision repair: DNA may be damaged by
chemicals, radiation, etc. Mechanism to cut
out and replace with correct bases
Mutations
 A mismatching of base pairs, can occur at a
rate of 1 per 10,000 bases.
 DNA polymerase proofreads and repairs
accidental mismatched pairs.
 Chances of a mutation occurring at any one
gene is over 1 in 100,000
 Because the human genome is so large,
even at this rate, mutations add up. Each of
us probably inherited 3-4 mutations!
Proofreading and Repairing DNA
 DNA polymerases 1 A thymine dimer
proofread newly made distorts the DNA molecule.
2 A nuclease enzyme cuts
DNA, replacing any the damaged DNA strand
at two points and the
incorrect nucleotides damaged section is
removed.
 In mismatch repair of DNA, Nuclease

repair enzymes correct DNA 3 Repair synthesis by

errors in base pairing polymerase a DNA polymerase
fills in the missing
 In nucleotide excision DNA nucleotides.

repair nucleases cut out DNA

ligase 4 DNA ligase seals the
and replace damaged Free end of the new DNA
To the old DNA, making the
stretches of DNA strand complete.
Protein Synthesis
 The information content of DNA is in the
form of specific sequences of nucleotides
along the DNA strands
 The DNA inherited by an organism leads
to specific traits by dictating the synthesis
of proteins
 The process by which DNA directs protein
synthesis, gene expression includes two
stages, called transcription and translation
Transcription and Translation
 Cells are governed by a cellular chain of
command
• DNA RNA protein
 Transcription
• Is the synthesis of RNA under the direction
of DNA
• Produces messenger RNA (mRNA)
 Translation
• Is the actual synthesis of a polypeptide,
which occurs under the direction of mRNA
• Occurs on ribosomes
Transcription
 Transcription is the DNA-
directed synthesis of RNA
 RNA synthesis
• Is catalyzed by RNA
polymerase, which pries the
DNA strands apart and hooks
together the RNA nucleotides
• Follows the same base-pairing
rules as DNA, except that in
RNA, uracil substitutes for
thymine
 RNA
 RNA is single stranded,
not double stranded
like DNA
 RNA is short, only 1
gene long, where DNA
is very long and
contains many genes
 RNA uses the sugar
ribose instead of
deoxyribose in DNA
 RNA uses the base
uracil (U) instead of
thymine (T) in DNA.
 Synthesis of an RNA Transcript
 The stages of
Promoter
Transcription unit
5
3 3
5

transcription RNA polymerase

Start point
DNA

1
Initiation. After RNA polymerase binds to
are the promoter, the DNA strands unwind, and
the polymerase initiates RNA synthesis at the
start point on the template strand.

• Initiation 5
3

Template strand of
3
5

• Elongation
Unwound RNA DNA
DNA transcript
2
Elongation. The polymerase moves downstream, unwinding the

• Termination Rewound
DNA and elongating the RNA transcript 5  3 . In the wake of
transcription, the DNA strands re-form a double helix.

RNA
5
3 3 3
5
5

RNA
transcript
3 Termination. Eventually, the RNA
transcript is released, and the
polymerase detaches from the DNA.

5
3 3
5

5 3
Completed RNA
transcript
Synthesis of an RNA Transcript - Initiation
TRANSCRIPTION DNA 1 Eukaryotic promoters
RNA PROCESSING Pre-mRNA

 Promoters signal the TRANSLATION

mRNA
Ribosome

initiation of RNA 5
Polypeptide

T A T A A AA
Promoter

3
synthesis 3 AT AT T T T

TATA box Start point Template

5

DNA strand

 Transcription factors 2 Several transcription

factors
Transcription
help eukaryotic RNA factors

5 3
polymerase recognize 3
3 Additional transcription
5

factors
promoter sequences
RNA polymerase II
Transcription factors

5 3
3 5 5
RNA transcript
Transcription initiation complex
Synthesis of an RNA Transcript - Elongation

 RNA polymerase Elongation Non-template

strand of DNA
synthesizes a single RNA nucleotides
strand of RNA against
the DNA template RNA
strand (anti-sense polymerase

strand), adding
nucleotides to the 3’ T C C A A
end of the RNA chain 3
A

3 end

 As RNA polymerase U

moves along the DNA 5

A E G C A
it continues to untwist
T
the double helix, A G G T T
exposing about 10 to
20 DNA bases at a 5
Direction of transcription
(“downstream”) Template
time for pairing with strand of DNA
RNA nucleotides
Newly made
RNA
Synthesis of an RNA Transcript - Termination

• Specific sequences in the DNA signal termination

of transcription
• When one of these is encountered by the
polymerase, the RNA transcript is released from
the DNA and the double helix can zip up again.
Transcription Overview
Post Termination RNA Processing

 Most eukaryotic mRNAs aren’t ready to be

translated into protein directly after being
transcribed from DNA. mRNA requires
processing.
 Transcription of RNA processing occur in the
nucleus. After this, the messenger RNA moves
to the cytoplasm for translation.
 The cell adds a protective cap to one end, and a
tail of A’s to the other end. These both function
to protect the RNA from enzymes that would
degrade
Post Termination RNA Processing

 Most of the genome consists of non-coding regions

called introns
• Non-coding regions may have specific chromosomal
functions or have regulatory purposes
• Introns also allow for alternative RNA splicing

 Thus, an RNA copy of a gene is converted into

messenger RNA by doing 2 things:
• Add protective bases to the ends
• Cut out the introns
 Alteration of mRNA Ends

 Each end of a pre-mRNA molecule is modified

in a particular way
• The 5 end receives a modified nucleotide
cap
• The 3 end gets a poly-A tail
A modified guanine nucleotide 50 to 250 adenine nucleotides
added to the 5 end added to the 3 end
TRANSCRIPTION DNA

RNA PROCESSING Pre-mRNA Protein-coding segment Polyadenylation signal

5
3
mRNA
G P P P AAUAAA AAA…AAA
Ribosome
TRANSLATION
Start codon Stop codon
5 Cap 5 UTR 3 UTR Poly-A tail
Polypeptide
RNA Processing - Splicing
 The original transcript
from the DNA is called
pre-mRNA.

 It contains transcripts of
both introns and exons.

 The introns are

removed by a process
called splicing to
produce messenger
RNA (mRNA)
RNA Processing
 Proteins often have a modular architecture consisting
of discrete structural and functional regions called
domains
 In many cases different exons code for the different
domains in a protein

Gene
DNA
Exon 1 Intron Exon 2 Intron Exon 3
Transcription
RNA processing
Translation

Domain 3

Domain 2
Domain 1

Figure 17.12 Polypeptide

 Translation
 Translation is the RNA- TRANSCRIPTION DNA

mRNA

directed synthesis of a TRANSLATION

Ribosome

Polypeptide

polypeptide
Amino
 Translation involves Polypeptide acids

• mRNA tRNA with

amino acid
• Ribosomes - Ribosome attached

Ribosomal RNA Gly

• Transfer RNA tRNA

• Genetic coding - A A A
Anticodon
U G G U U U G G C

codons 5 Codons 3
mRNA
The Genetic Code

 Genetic information is encoded as a sequence

of non-overlapping base triplets, or codons
DNA Gene 2
molecule
Gene 1
Gene 3

DNA strand 3 5
(template) A C C A A A C C G A G T

TRANSCRIPTION

U G G U U U G G C U C A
mRNA 5 3
Codon
TRANSLATION

Protein Trp Phe Gly Ser

Amino acid
 The Genetic Code
 Codons: 3 base code for the production of a specific
amino acid, sequence of three of the four different
nucleotides

 Since there are 4 bases and 3 positions in each codon,

there are 4 x 4 x 4 = 64 possible codons

 64 codons but only 20 amino acids, therefore most have

more than 1 codon

 3 of the 64 codons are used as STOP signals; they are

found at the end of every gene and mark the end of the
protein

 One codon is used as a START signal: it is at the start of

every protein
The Genetic Code
 A codon in messenger RNA is either translated into an amino acid
or serves as a translational start/stop signal
Second mRNA base
U C A G
UUU UCU UAU UGU U
Phe Tyr Cys
UAC
U UUC UCC
Ser
UGC C
UUA UCA UAA Stop UGA Stop A
Leu UAG Stop UGG Trp G
UUG UCG

Third mRNA base (3 end)

First mRNA base (5 end)

CUU CCU CAU CGU U

His
CUC CCC CAC CGC C
C Leu Pro Arg
CUA CCA CAA CGA A
Gln
CUG CCG CAG CGG G
AUU ACU AAU AGU U
Asn
A
AUC lle ACC AAC AGC Ser C
Thr
AUA ACA AAA AGA A
Met or Lys Arg
AUG start ACG AAG AGG G
GUU GCU GAU GGU U
G GUC GCC GAC Asp GGC C
Val Ala Gly
GUA GCA GAA GGA A
GUG GCG GAG Glu GGG G
 Transfer RNA

 Consists of a single RNA strand that is only about 80 nucleotides long

 Each carries a specific amino acid on one end and has an anticodon on the
other end
 A special group of enzymes pairs up the proper tRNA molecules with their
corresponding amino acids.
 tRNA brings the amino acids to the ribosomes,

3
Amino acid A
C
attachment site C
A 5
C G
The “anticodon” is the 3 RNA bases that G C
C G
matches the 3 bases of the codon on the U G
U A
mRNA molecule A U
U C A U
* C A C AG UA A G *
G * C U C
G U G U G
*
C * C G A G
* * U C * A G G
* G AG C
(a) Two-dimensional structure. The four base-paired regions and three G C Hydrogen
loops are characteristic of all tRNAs, as is the base sequence of the U A bonds
amino acid attachment site at the 3 end. The anticodon triplet is * G
A
unique to each tRNA type. (The asterisks mark bases that have been A* C
chemically modified, a characteristic of tRNA.) * U
A G
A
Anticodon
 Transfer RNA
 3 dimensional tRNA molecule is roughly “L” shaped

5 Amino acid
attachment site
3

Hydrogen
bonds

A AG

3 5
Anticodon
Anticodon
(c) Symbol used
(b) Three-dimensional structure in the book
 Ribosomes

 Ribosomes facilitate the specific coupling of tRNA anticodons with

mRNA codons during protein synthesis
 The 2 ribosomal subunits are constructed of proteins and RNA
molecules named ribosomal RNA or rRNA

TRANSCRIPTION DNA

mRNA
Ribosome
TRANSLATION

Polypeptide
Exit tunnel
Growing
polypeptide
tRNA
molecules
Large
subunit
E
P A

Small
subunit

5
mRNA 3
(a) Computer model of functioning ribosome. This is a model of a bacterial
ribosome, showing its overall shape. The eukaryotic ribosome is roughly
similar. A ribosomal subunit is an aggregate of ribosomal RNA molecules
and proteins.
 Building a Polypeptide
Amino end Growing polypeptide

Next amino acid

to be added to
polypeptide chain

tRNA

mRNA 3

Codons
5

(c) Schematic model with mRNA and tRNA. A tRNA fits into a binding site when its anticodon base-
pairs with an mRNA codon. The P site holds the tRNA attached to the growing polypeptide. The A
site holds the tRNA carrying the next amino acid to be added to the polypeptide chain. Discharged
tRNA leaves via the E site.
Building a Polypeptide
 We can divide translation into three stages
• Initiation
• Elongation
• Termination
 The AUG start codon is recognized by methionyl-tRNA or Met
 Once the start codon has been identified, the ribosome
incorporates amino acids into a polypeptide chain
 RNA is decoded by tRNA (transfer RNA) molecules, which each
transport specific amino acids to the growing chain
 Translation ends when a stop codon (UAA, UAG, UGA) is reached
Initiation of Translation

 The initiation stage of translation brings together mRNA, tRNA

bearing the first amino acid of the polypeptide, and two subunits
of a ribosome

Large
ribosomal
P site subunit
3 U A C 5
5 A U G 3

Initiator tRNA
GTP GDP
E A
mRNA
5 3 5 3
Start codon

mRNA binding site Small Translation initiation complex

ribosomal
subunit

1 2
A small ribosomal subunit binds to a molecule of
mRNA. In a prokaryotic cell, the mRNA binding site
on this subunit recognizes a specific nucleotide
sequence on the mRNA just upstream of the start
codon. An initiator tRNA, with the anticodon UAC,
base-pairs with the start codon, AUG. This tRNA
carries the amino acid methionine (Met).
The arrival of a large ribosomal subunit completes
the initiation complex. Proteins called initiation
factors (not shown) are required to bring all the
translation components together. GTP provides
the energy for the assembly. The initiator tRNA is
in the P site; the A site is available to the tRNA
bearing the next amino acid.
Elongation of the Polypeptide Chain

 In the elongation stage, amino acids are added one by one to

the preceding amino acid
1 Codon recognition. The anticodon
TRANSCRIPTION DNA
Amino end of an incoming aminoacyl tRNA
mRNA
of polypeptide base-pairs with the complementary
Ribosome
TRANSLATION mRNA codon in the A site. Hydrolysis
Polypeptide
of GTP increases the accuracy and
E efficiency of this step.
mRNA 3
Ribosome ready for P A
next aminoacyl tRNA 5 site site
2 GTP
2 GDP

E E

P A P A

2 Peptide bond formation. An

GDP
3 Translocation. The ribosome rRNA molecule of the large
GTP
subunit catalyzes the formation
translocates the tRNA in the A
of a peptide bond between the
site to the P site. The empty tRNA
new amino acid in the A site and
in the P site is moved to the E site, E
the carboxyl end of the growing
where it is released. The mRNA
polypeptide in the P site. This step
moves along with its bound tRNAs, P A attaches the polypeptide to the
bringing the next codon to be
tRNA in the A site.
translated into the A site.
Termination of Translation
 The final stage is termination when the ribosome reaches a stop codon
in the mRNA

Release
factor
Free
polypeptide

5
3 3
3
5 5
Stop codon
(UAG, UAA, or UGA)
1 When a ribosome reaches a stop 2 The release factor hydrolyzes 3 The two ribosomal subunits
codon on mRNA, the A site of the the bond between the tRNA in and the other components of
ribosome accepts a protein called the P site and the last amino the assembly dissociate.
a release factor instead of tRNA. acid of the polypeptide chain.
The polypeptide is thus freed
from the ribosome.
Translation
 The final step in translation is termination. When the
ribosome reaches a STOP codon, there is no
corresponding transfer RNA.
 Instead, a small protein called a “release factor” attaches
to the stop codon.
 The release factor causes the whole complex to fall
apart: messenger RNA, the two ribosome subunits, the
new polypeptide.
 The messenger RNA can be translated many times, to
produce many protein copies.
Post-translation
 The new polypeptide is now floating loose in the
cytoplasm if translated by a free ribosme.
 It might also be inserted into a membrane, if
translated by a ribosome bound to the
endoplasmic reticulum.
 Polypeptides fold spontaneously into their active
configuration, and they spontaneously join with
other polypeptides to form the final proteins.
 Sometimes other molecules are also attached to
the polypeptides: sugars, lipids, phosphates, etc.
All of these have special purposes for protein
function.
A summary of transcription and translation in a eukaryotic cell
TRANSCRIPTION DNA
1RNA is transcribed
from a DNA template.
3

5 RNA RNA
transcript polymerase
RNA PROCESSING Exon
2
In eukaryotes, the RNA transcript
RNA transcript (pre- (pre-mRNA)
mRNA) is spliced and Intron
modified to produce
mRNA, which moves Aminoacyl-tRNA
from the nucleus to the synthetase
cytoplasm. NUCLEUS

Amino
FORMATION OF acid
INITIATION COMPLEX AMINO ACID ACTIVATION
CYTOPLASM tRNA
3 After leaving the 4
Each amino acid
nucleus, mRNA attaches attaches to its proper tRNA
to the ribosome. with the help of a specific
enzyme and ATP.
mRNA Growing
polypeptide
Activated
amino acid

Ribosomal
subunits

5
TRANSLATION
5
A succession of tRNAs
E A add their amino acids to
Anticodon the polypeptide chain
A A A
as the mRNA is moved
U G G U U U A U G
through the ribosome
one codon at a time.
Figure 17.26 Codon (When completed, the
polypeptide is released
Ribosome from the ribosome.)