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Transcript
The RNA
 Three major classes of RNA: messenger (mRNA),
transfer (tRNA) and ribosomal (rRNA). Minor
classes of RNA include small nuclear RNA; small
nucleolar RNA;……….
 RNA is a single stranded; the pyrimidine base uracil
(U) replaces thymine and ribose sugar replaces
deoxyribose.
Dr./Salwa Hassan Teama 2012
Messenger RNA/ mRNA
• Transcripts of structural genes.
• Encode all the information necessary for the synthesis
of a polypeptide of protein.
• The 5' terminus is capped by 7 methyguanosine
triphosphate.
• Synthesis of the poly (A) tail involves cleavage of its
3' end and then the addition of about 200 adenine
residues.
• Intermediate carrier of genetic information; deliver
genetic information to the cytoplasm.
mRNA
Transfer RNA/ tRNA
 All the tRNAs share a
common secondary structure
resembles a cloverleaf: They have four base- paired
stems defining three stem-loops (the D loop,
anticodon loop, and T loop) and the acceptor stem.
 tRNA carry correct amino acids to their position
along the mRNA template to be added to the growing
polypeptide chain.
Dr./Salwa Hassan Teama 2012
tRNA
Ribosomal RNA/ rRNA
• The central component of the ribosome.
• Ribosome; factory for protein synthesis; composed of
ribosomal RNA and ribosomal proteins (known as a
Ribonucleoproteinor RNP).
• rRNA provides a mechanism for decoding mRNA
into amino acids.
Dr./Salwa Hassan Teama 2012
General Structure of Nucleic Acid
DNA and RNA are long
chain polymers of small
chemical compound called
nucleotides.
Dr./Salwa Hassan Teama 2012
Nucleotides
Nucleotides; ring shaped structures composed of:
 Nitrogenous base; these bases are classified based on
their chemical structures into two groups:
 Purine; double ringed structure (Adenine and Guanine).
 Pyrimidine; single ring structures (cytosine and thymine).
 Sugar
 Phosphate group
Dr./Salwa Hassan Teama 2012
Nucleotides
• DNA: Four different types of nucleotides differ in
nitrogenous base:

A is for adenine;

G is for guanine;

C is for cytosine and

T is for thymine.
 RNA: thymine base replaced by uracil base.
Dr./Salwa Hassan Teama 2012
Nucleotides
Jypx35. Source: Wikipedia
The DNA
 Deoxyribonucleic Acid (DNA); the genetic material
of all cellular organisms and most viruses.
 DNA; the gigantic molecule which is used to encode
genetic information for all life on Earth.
 A human cell contains about 2 meters of DNA. DNA
in the body could stretch to the sun and back almost 100
times. So it is tightly packed.
 DNA responsible for preserving, copying and
transmitting information within cells and from
generation to generation.
Dr./Salwa Hassan Teama 2012
DNA Double Helix
 Linked as a twisted ladder.
 The curving sides of the ladder represent the
sugar-phosphate backbone of the two DNA
strands; the rungs are the base pairs.
 Possess antiparallel polarity.
 Stabilized by hydrogen bonds between the
bases.
Dr./Salwa Hassan Teama 2012
DNA Double Helix
Madprime. Source: Wikipedia
DNA Structure
DNA is a nucleic acid.
The building blocks of DNA are nucleotides,
each composed of:
– a 5-carbon sugar called deoxyribose
– a phosphate group (PO4)
– a nitrogenous base
• adenine, thymine, cytosine, guanine
14
15
DNA Structure
The nucleotide structure consists of
– the nitrogenous base attached to the 1’ carbon of
deoxyribose
– the phosphate group attached to the 5’ carbon of
deoxyribose
– a free hydroxyl group (-OH) at the 3’ carbon of
deoxyribose
16
17
DNA Structure
Nucleotides are connected to each other to
form a long chain
phosphodiester bond: bond between adjacent
nucleotides
– formed between the phosphate group of one
nucleotide and the 3’ –OH of the next nucleotide
The chain of nucleotides has a 5’ to 3’
orientation.
18
19
DNA Structure
Determining the 3-dimmensional structure of DNA
involved the work of a few scientists:
– Erwin Chargaff determined that
• amount of adenine = amount of thymine
• amount of cytosine = amount of guanine
This is known as Chargaff’s Rules
20
DNA Structure
Rosalind Franklin and Maurice Wilkins
– Franklin performed X-ray diffraction studies to
identify the 3-D structure
– discovered that DNA is helical
– discovered that the molecule has a diameter of
2nm and makes a complete turn of the helix every
3.4 nm
21
DNA Structure
James Watson and Francis Crick, 1953
– deduced the structure of DNA using evidence
from Chargaff, Franklin, and others
– proposed a double helix structure
22
DNA Structure
The double helix consists of:
– 2 sugar-phosphate backbones
– nitrogenous bases toward the interior of the
molecule
– bases form hydrogen bonds with complementary
bases on the opposite sugar-phosphate backbone
23
DNA Structure
The two strands of nucleotides are antiparallel
to each other
– one is oriented 5’ to 3’, the other 3’ to 5’
The two strands wrap around each other to
create the helical shape of the molecule.
24
25
DNA Replication
Matthew Meselson & Franklin Stahl, 1958
investigated the process of DNA replication
considered 3 possible mechanisms:
– conservative model
– semiconservative model
– dispersive model
26
27
DNA Replication
•
DNA replication is the process of copying a DNA molecule. Replication is
semiconservative, with each strand of the original double helix (parental molecule)
serving as a template (mold or model) for a new strand in a daughter molecule. This
process consists of:
• Unwinding (initiation): old strands of the parent DNA molecule are unwound as
weak hydrogen bonds between the paired bases are “unzipped” and broken by the
enzyme helicase.
• Complementary base pairing (elongation): free nucleotides present in the nucleus
bind with complementary bases on unzipped portions of the two strands of DNA;
this process is catalyzed by DNA polymerase.
• Joining (elongation): complementary nucleotides bond to each other to form new
strands; each daughter DNA molecule contains an old strand and a new strand; this
process is also catalyzed by DNA polymerase.
• termination – replication is terminated differently in prokaryotes and eukaryotes
Ends in prokaryotes when origin is reached
Ends in eukaryotes when telomere is reached
telomeres – repeated DNA sequence on the ends of eukaryotic
chromosomes
•
DNA replication must occur before a cell can divide; in cancer, drugs with molecules
similar to the four nucleotides are used to stop replication.
28
DNA replication
30
(2) Chromosomes
Thousands of genes per cell –
Genes are a segment of DNA
that produce a biologically active product
2 of each chromosome per cell
– one maternal, one paternal
Histones have high contents
of Arg, Lys
48-240 million base pairs
per chromosome
The Gene
 The gene; it is a segment within a very long strand of
DNA.
 Genes are the basic units of hereditary.
 Genes located on chromosome on its place or locus.
 Allele; a variant of the DNA sequence at a given
locus. Each allele inherited from a different parent.
Dr./Salwa Hassan Teama 2012
The Gene
Source: National Human Genome Research Institute.
Gene Structure
• Most of the genes consist of; short coding
sequences or exons are interrupted by a longer
intervening noncoding sequence or introns;
although a few genes in the human genome
have no introns.
Dr./Salwa Hassan Teama 2012
Genes
• Genes are the basic physical and functional
units of heredity. Each gene is located on a
particular region of a chromosome and has a
specific ordered sequence of nucleotides (the
building blocks of DNA).
Exons vs Introns
• Eukaryotic genes have introns and exons. Exons
contain nucleotides that are translated into amino
acids of proteins. Exons are separated from one
another by intervening segments of junk DNA called
introns. Introns do not code for protein. They are
removed when eukaryotic mRNA is processed. Exons
make up those segments of mRNA that are spliced
back together after the introns are removed; the
intron-free mRNA is used as a template to make
proteins.
Splicing
• Exons are sequences of DNA that are expressed3into
protein.
• Introns are intervening sequences that are not
translated into protein
C
DNA
1
2
Pre-mRNA
1
2
Spliced mRNA
1
2
C
C
3
3
3
Exons and Coding
What’s the difference between exons and coding
sequence?
Exons often are described as short segments of protein
coding sequence. This is a bit of an oversimplification.
Exons are those segments of sequence that are spliced
together after the introns have been removed from the
pre-mRNA. Yes, the coding sequence is contained in
exons, but it is possible for some exons to contain no
coding sequence. Portions of exons or even entire exons
may contain sequence that is not translated into amino
acids. These are the untranslated regions or UTRs.
UTRs are found upstream and downstream of the
protein-coding sequence.
Genetic Mutation
A mutation is a change in
the DNA sequence or
arrangement of DNA.
Yassine Mrabet . Source:Wikipedia
Dr./Salwa Hassan Teama 2012
Mutations can change the meaning
of genes
• Mutations are changes in the DNA base
sequence
– caused by errors in DNA replication or by mutagens
– change of a single DNA nucleotide causes sickle-cell
disease
RNA
TACTCT
ATGAGA
TACTCT
ATGAGA
3’
5’
PROMOTER
DNA
exon 1
template
5’
3’
exon 2
exon 3
ATG
TAA AATAAA
TRANSCRIPTION
intron
Pre-mRNA
intron
AUG
UAA AAUAAA
RNA SPLICING
mRNA
AUG
UAA AAUAAA
coding sequence
TRANSLATION
protein
MAPSSRGG…..
Normal hemoglobin DNA
mRNA
Mutant hemoglobin DNA
mRNA
Normal hemoglobin
Sickle-cell hemoglobin
Glu
Val
Figure 10.16A
• Types of mutations
NORMAL GENE
mRNA
Protein
Met
Lys
Phe
Gly
Ala
Lys
Phe
Ser
Ala
BASE SUBSTITUTION
Met
Missing
BASE DELETION
Met
Lys
Leu
Ala
His
Figure 10.16B