mRNA Protein

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Transcript mRNA Protein

transcription
The first step of gene expression – synthesis of RNA molecule
Some nomenclature conventions
RNAP
RNA
DNA
Similarities and Differences Between DNA and RNA
RNA
• Similar strand structure
• Can define a 5’ and 3’ end
• 2’ hydroxyl in RNA: causes
stability differences)
• Uracil in RNA takes the
place of Thymine in in DNA
DNA
Secondary structure of RNA
Stem &
loop
Difference between DNA and
RNA.
– DNA – Double Helix, RNA – Single Stranded
– DNA --- A-T, RNA ---A-U
– DNA ---Deoxyribose Sugar, RNA---Ribose
• What is a similarity of DNA and RNA?
– G binds with C in both DNA and RNA
– Both have sugar and phosphate backbone
The pathway of gene expression
CAP
Conserved seqences
Polypyrimidine tract
‫גן הבטא גלובין‬
‫ההומני‬
Splice sites can be included in the exons
mRNA splicing
lariat
‫‪spliceosome‬‬
‫מעגל‬
‫מחזורי‬
‫של‬
‫ראקציית‬
‫השיחבור‬
‫ספליסוזום‬
Systemic Lupus Erythematosus (SLE)
Lupus is a type of immune system disorder known as an autoimmune disease. In
autoimmune diseases, the body harms its own healthy cells and tissues. This leads to
inflammation and damage of various body tissues. Lupus can affect many parts of the
body, including the joints, skin, kidneys, heart, lungs, blood vessels, and brain.
Although people with the disease may have many different symptoms, some of the most
common ones include extreme fatigue, painful or swollen joints (arthritis), unexplained
fever, skin rashes, and kidney problems. Lupus is also known as a rheumatic disease.
The rheumatic diseases are a group of disorders that cause aches, pain, and stiffness in
the joints, muscles, and bones.
15% of the mutation leading to genetic disorders effect splicing activity
Untreated β thalassemia
Treatment of thalassemia major
antisense
Human genome
2.91 billion base pairs
24,500 genes
1.5% exons (127 nucleotides)
24% introns (~3,000 nucleotides)
75% intergenic (no genes)
Average size of a gene is 27,894 bases
Contains an average of 8.8 exons
Titin contains 234 exons.
Gene number
C. elegans
~19,000
Drosophila melanogaster
~13,600
Arabidopsis thaliana
~25,500
Homo Sapiens
~24,000
Mouse
~24,000
Rice (Oryza sativa)
~50,000
Compared to
worm and fly,
human has
shorter exons
and longer
introns on the
extremes of the
distribution
150 nt – drosophila
125 nt – Ciona intes.
119 nt - human
5000 genes
234 introns
Multi-introns genes
7.8 introns per gene
Sequences of
humanmouse
homologous
exons are
88%
conserved
Alternative
Alternative splicing
splicing
‫פוליפרימידין טראק‬
40%
18%
8%
?
3%
isoform
‫‪18‬‬
‫איזופורמים‬
‫‪1‬‬
Alternative splicing regulate pro or
anti apoptotic pathways.
pro-apoptotic
anti-apoptotic
translation
The last stage in gene expression – synthesis of protein
Amino acid
N
C
N to C terminal
5’ to 3’
CDS
Aminoacyl tRNA
tRNA
Aminoacyl-tRNA •
20( synthetase
)diffrent
one for each amino –
acid
NEEDS ENERGY! –
64 combinations for 20 amino acids
3 termination codons
‫סרט טרנסלציה‬
‫ספירת מלאי‬
Met one codon
LEU 6 codons, 4 of which are CUN
Disease-Associated Mutations
A mutation is a change in the normal base pair
sequence
Commonly used to define DNA sequence
changes that alter protein function
Polymorphism
DNA sequence changes that do not alter
protein function (common definition, not technically
correct)
Functional protein
Functional protein
Single nucleotide polymorphisms
(SNP) (in the coding sequence)
mRNA
Normal
A U G
Protein
Sequenc
e variant
Met
A A G U U U GGC GC A U UG C A A
Lys
Phe
Gly
Ala
Leu
Gln
mRNA
A U G
Protein
Met
A A G U U U GGU GC A U UG C A A
Lys
Phe
Gly
Ala
Silent DNA sequence polymorphism
Leu
Gln
Missense Mutations
Normal
mRNA
A U G
Protein
Met
A A G U U U GGC GC A U UG C A A
Lys
Phe
Gly
Ala
Leu
Gln
mRNA
Missense
A U G
Protein
Met
A A G U U U AGC GC A U UG C A A
Lys
Phe
Ser
Ala
Missense: changes to a codon for another amino
acid (can be harmful mutation or neutral
polymorphism)
Leu
Gln
Nonsense Mutations
Normal
mRNA
A U G
Protein
Met
A A G U U U GGC GC A U UG C A A
Lys
Phe
Gly
Ala
Leu
Gln
mRNA
A U G
Nonsense
Protein
U A G U U U GGC GC A U UG C A A
Met
Nonsense: change from an amino acid codon to a
stop codon, producing a shortened protein
Frameshift Mutations
Normal
mRNA
A U G
Protein
Frameshift
Met
A A G U U U GGC GC A U UG C A A
Lys
Phe
Gly
Ala
Leu
Gln
mRNA
A U G A A G U U G GC G C A U UGC A A
Protein
Met
Lys
Leu
Ala
Frameshift: insertion or deletion of base pairs, producing
a stop codon downstream and (usually) shortened protein
Pre-mature stop codon
mutation
Missense mutation
Translation II
A peptide – a chain of amino acids
A protein – a stretch of one or more amino acid chains with biological function
+eIF3
eIF3
Translation
‫סרט טרנסלציה‬
Life cycle of mRNA movie