Regulation of gene expression III. tRNA synthesis, aminoacyl activation, translation, translation...
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Regulation of gene expression III.
tRNA synthesis, aminoacyl activation, translation, translation inhibitors,
molecular genetics of deseases and diagnostic methods
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The genetic code
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The structure of transfer RNA
Ψ: pseudouridine D: dihydrouridineDownloaded from www.pharmacy123.blogfa.com
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Activation of aminoacids
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Comparison of ribosomes
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Initiation of translation
1. Peptidyl-transferase
2. EF-G (translocase)
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Elongation
1. EF-Tu + GTP= EF-Tu-GDP + Pi
EF-Ts
EF-Tu + GDP
Important time delay for accuracy
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Termination
Binding of releasing factor to STOP
Termination
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Translation on the surface and processing in the lumen of ER
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The recognition of signal peptide
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Double transmembrane domain
Stop-transfer sequence
Start-transfer sequence
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Multiple transmembrane domain
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Differences in the pro-and eucaryotic mRNA
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The procaryotic translation
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Regulation of translation initiation
• dsRNA dependent protein kinase phosphorylates eIF, this inhibits initiation
• Viral interferon stimulated dsRNA dependent protein kinase (initial stage of infection:-RNA, +RNA or RNA:RNA hybrid)
• Reticulocyte protein kinase: inhibited by hem – no hem, no protein synthesis (90% globin)
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The effect of antibiotics on procaryotic translation
• Steptomycin – inhibition of initiation, misreading of the code (resistance: mutation in the S12 ribosomal protein) Neomycin, gentamycin similarly
• Tetracycline – inhibits a. ac. tRNA binding to ribosome
• Chloramphenicol – inhibits pepidyl transferase
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Eucaryotic translation specific inhibitors
• Puromycin – prevents tRNA binding to ribosome and incorporates into peptide chain, cause premature termination
• Cycloheximide – specific for eucaryotes, chloramphenicol-like effect
• Diptheria (corynebacterium exotoxin) the elF2 is inactivated by ADP-ribosilation made by the toxin
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DNA chip
Green: less than average exp.
red: more than average exp.
black: close to average exp.
Differential analysis of mRNA levels of 1800 genes on cDNA array
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Differential analysis of protein expression
pH2 pH12
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Fluorescence-activated cell sorter
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Sequencing I
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Sequencing II.
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Sequencing III.
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RNA interference
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Genetic diseases
• 4000 diseases have genetic base• 10% of hospitalised children• Many chronic diseases have genetic component
(diabetes melitus, athelosclerosis)• Chromosomal - trisomy of 21 – Down’s
syndrome (karyotype – chromosomal translocations – positional effect)
• Monogenic disorders (autosomal dominant – recessive – X-linked)
• Multifactorial dirorders (ishemic heart disease, hypertension)
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Pedigree analysis
T to A change in the -globin gene – sickle cell anemia
SS homozygous
AS heterozygous (prenatal)
AA homozygous
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