Transcript Document 7380490

From DNA to
Proteins
Chapter 15
Functions of DNA
Heredity: passing on traits from parents to
offspring
Replication
 Coding for our traits by containing the
information to make proteins
Protein Synthesis

 Transcription
 Translation
Genes
Genes are units of DNA that code to make
a single polypeptide (protein)
 Found within specific location on the
chromosomes (loci)
 Humans have >30,000 genes
 How do we make a protein from the
information in a gene?

Steps of Protein synthesis
Same two steps produce all proteins:
1) Transcription:

DNA (Gene) is transcribed to form
messenger RNA (mRNA)
 Occurs in the nucleus
2) Translation:

mRNA is translated to form polypeptide
chains, which fold to form proteins
 Occurs in ribosomes which are in the
cytoplasm
Transcription and Translation
RNA vs. DNA
DNA
RNA
Number of
strands
Two
One
Nucleotides
ATGC
AUGC
Sugar
Deoxyribose
Ribose
Location
Nucleus only
Nucleus and
Cytoplasm
Three Classes of RNAs

Messenger RNA (mRNA)
 Carries

Ribosomal RNA (rRNA)
 Major

protein-building instruction
component of ribosomes
Transfer RNA (tRNA)
 Delivers
amino acids to ribosomes
A Nucleotide Subunit of RNA
uracil (base)
phosphate
group
sugar
(ribose)
Figure 14.2
Page 228
Transcription
DNA  RNA
 Occurs in the nucleus
 Requires the enzyme RNA Polymerase
 Consists of 3 steps:
 Initiation
 Elongation
 Termination

RNA Polymerases

No primers needed to start complementary
copy

RNA is made in the 5´→ 3´ direction
 DNA
template strand is 3´→ 5´
Steps of Transcription: Initiation

RNA Polymerase binds to Promoter
 Promoter:
A base sequence in the DNA that
signals the start of a gene

DNA is unwound
 i.e.
hydrogen bonds are broken
Transcription: Initiation
Steps of Transctription: Elongation
RNA ploymerase adds complementary
RNA nucleotides to one strand of DNA –
Template strand
 Forms Pre-mRNA

Transcription: Elongation
Steps of Transcription: Termination

When mRNA synthesis is complete, RNA
Polymerase falls off of DNA, RNA is
released from DNA, and DNA rewinds
Transcription: Termination
Transcription vs. DNA Replication

Like DNA replication
 Nucleotides

added in 5’ to 3’ direction
Unlike DNA replication
 Only
small stretch is template
 RNA
polymerase catalyzes nucleotide
addition
 Product
is a single strand of RNA
Production of mRNAs in
Eukaryotes
Eukaryotic protein-coding genes are
transcribed into precursor-mRNAs that are
modified in the nucleus
 Introns are removed during pre-mRNA
processing to produce the translatable
mRNA
 Introns contribute to protein variability

Messenger RNA

Prokaryotes
 Coding
region flanked by 5´ and 3´
untranslated regions

Eukaryotes
 Coding
region flanked by 5´ and 3´
untranslated regions (as in prokaryotes)
 Additional noncoding elements
Eukaryotic Pre-mRNA

Precursor-mRNA (pre-mRNA)
 Must
be processed in nucleus to produce
translatable mRNA

5´ cap
 Reversed
guanine-containing nucleotide
 Site where ribosome attaches to mRNA

Poly(A) tail
 50
to 250 adenine nucleotides added to 3´
end
 Protects mRNA from RNA-digesting enzymes
Eukaryotic Pre-mRNA

Introns
 Non-protein-coding
sequences in the pre-
mRNA
 Must be removed before translation

Exons
 Amino
acid coding sequences in pre-mRNA
 Joined together sequentially in final mRNA
RNA
Processing
mRNA Splicing
Introns in pre-mRNAs removed
 Spliceosome

 Pre-mRNA
 Small
ribonucleoprotein particles (snRNP)
Small nuclear RNA (snRNA) + several proteins
 Bind to introns
 Loop introns out of the pre-mRNA,
 Clip the intron at each exon boundary
 Join adjacent exons together

mRNA
Splicing
Why are Introns Present?

Alternative splicing
 Different

versions of mRNA can be produced
Exon shuffling
 Generates
new proteins
Alternative Splicing

Exons joined in different combinations to
produce different mRNAs from the same
gene

Different mRNA versions translated into
different proteins with different functions

More information can be stored in the DNA
Alternative mRNA Splicing

α-tropomyosin in smooth and striated
muscle
The next step: Translation




“Translating” from nucleic acid (DNA/RNA)
“language” (nucleotides) to protein “language”
(amino acids)
Occurs in the ribosome within the cytoplasm
Requires tRNA – transfer RNA
How does the mRNA (and DNA) code for
proteins?
The Genetic Code
Genetic Code

Information
4
nucleotide bases in DNA or RNA sequences

 20

DNA: A,T,G,C
RNA: A,U,G,C
different amino acids in polypeptides
Code
 One-letter
words: only 4 combinations
 Two-letter words: only 16 combinations
 Three-letter words: 64 combinations
Genetic Code

DNA
 Three-letter

code: triplet
RNA
 Three-letter
code: codon
Genetic Code
Features of the Genetic Code

Sense codons
 61
codons specify amino acids
 Most amino acids specified by several codons
(degeneracy or redundancy)
 Ex: CCU, CCC, CCA, CCG all specify proline

Start codon or initiator codon
 First
amino acid recognized during translation
 Specifies amino acid methionine
Features of the Genetic Code

Stop codons or termination codons
 End
of a polypeptide-encoding mRNA
sequence
 UAA, UAG, UGA

Commaless
 Nucleic
acid codes are sequential
 No commas or spaces between codons
 Start codon AUG establishes the reading
frame
The Genetic Code
Genetic Code is Universal

Same codons specify the same amino
acids in all living organisms and viruses
 Only

a few minor exceptions
Genetic code was established very early in
the evolution of life and has remained
unchanged
Translation Overview
Translation
Purpose
 To “translate” from nucleic acid “language”
to protein “language”
 RNAprotein
What is needed for translation?
 mRNA transcript (processed)
 tRNAs
 Ribosomes
tRNAs

Transfer RNAs (tRNA)
 Bring
specific amino acids to ribosome
 Cloverleaf shape

Bottom end of tRNA contains anticodon
sequence that pairs with codon in mRNAs
tRNA Structure
Ribosomes

Made of ribosomal RNA (rRNA) and
proteins
 Two
subunits: large and small
Translation Stages

Initiation
 Ribosome
assembled with mRNA molecule
and initiator methionine-tRNA

Elongation
 Amino
acids linked to tRNAs added one at a
time to growing polypeptide chain

Termination
 New
polypeptide released from ribosome
 Ribosomal subunits separate from mRNA
Initiation

Initiator tRNA (Met-tRNA) binds to small
subunit
Initiation

Complex binds to 5´ cap of mRNA, scans
along mRNA to find AUG start codon
Initiation

Large ribosomal subunit binds to complete
initiation
Elongation



tRNA matching the next codon enters A site
carrying its amino acid
A peptide bond forms between the first and
second amino acids, which breaks the bond
between the first amino acid and its tRNA
Ribosome moves along mRNA to next codon
 Empty
tRNA moves from P site to E site, then released
 Newly formed peptidyl-tRNA moves from A site to P
site
 A site empty again
Elongation
Termination
Begins when A site reaches stop codon
 Release factor (RF) or termination factor
binds to A site
 Polypeptide chain released from P site
 Remaining parts of complex separated

Termination
What Happens to the
New Polypeptides?

Some just enter the cytoplasm

Many enter the endoplasmic reticulum and
move through the cytomembrane system
where they are modified
Transcription
Gene
Expression
Summary:
mRNA
Mature mRNA
transcripts
Translation
rRNA
ribosomal
subunits
tRNA
mature
tRNA
Gene Mutations

Changes in genetic material

Base-pair mutations change DNA triplet
 Results
in change in mRNA codon
 May lead to changes in the amino acid
sequence of the encoded polypeptide
Gene Mutation Types
Missense mutation
 Nonsense mutation
 Silent mutation
 Frameshift mutation

Missense Mutation

Changes one sense codon to one that
specifies a different amino acid
Sickle-Cell Anemia

Caused by a single missense mutation
Nonsense Mutation

Changes a sense codon to a stop codon
Silent Mutation

Changes one sense codon to another
sense codon that specifies the same
amino acid
Frameshift Mutation

Base-pair insertion or deletion alters the
reading frame after the point of the
mutation
Mutation Rates
Each gene has a characteristic mutation
rate
 Average rate for eukaryotes is between
10-4 and 10-6 per gene per generation
 Only mutations that arise in germ cells can
be passed on to next generation

Mutagens

Ionizing radiation (X rays)

Nonionizing radiation (UV)

Natural and synthetic chemicals