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Regulation of gene expression III. tRNA synthesis, aminoacyl activation, translation, translation inhibitors, molecular genetics of deseases and diagnostic.

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Presentation on theme: "Regulation of gene expression III. tRNA synthesis, aminoacyl activation, translation, translation inhibitors, molecular genetics of deseases and diagnostic."— Presentation transcript:

1 Regulation of gene expression III. tRNA synthesis, aminoacyl activation, translation, translation inhibitors, molecular genetics of deseases and diagnostic methods Downloaded from www.pharmacy123.blogfa.com

2 The genetic code Downloaded from www.pharmacy123.blogfa.com

3 The structure of transfer RNA Ψ: pseudouridineD: dihydrouridine Downloaded from www.pharmacy123.blogfa.com

4 Activation of aminoacids Downloaded from www.pharmacy123.blogfa.com

5 Comparison of ribosomes Downloaded from www.pharmacy123.blogfa.com

6 Initiation of translation 1. Peptidyl- transferase 2. EF-G (translocase) Downloaded from www.pharmacy123.blogfa.com

7 Elongation 1. EF-Tu + GTP= EF-Tu-GDP + Pi EF-Ts EF-Tu + GDP Important time delay for accuracy Downloaded from www.pharmacy123.blogfa.com

8 Termination Binding of releasing factor to STOP Termination Downloaded from www.pharmacy123.blogfa.com

9 Translation on the surface and processing in the lumen of ER Downloaded from www.pharmacy123.blogfa.com

10 The recognition of signal peptide Downloaded from www.pharmacy123.blogfa.com

11 Double transmembrane domain Stop-transfer sequence Start-transfer sequence Downloaded from www.pharmacy123.blogfa.com

12 Multiple transmembrane domain Downloaded from www.pharmacy123.blogfa.com

13 Differences in the pro-and eucaryotic mRNA Downloaded from www.pharmacy123.blogfa.com

14 The procaryotic translation Downloaded from www.pharmacy123.blogfa.com

15 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) Downloaded from www.pharmacy123.blogfa.com

16 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 Downloaded from www.pharmacy123.blogfa.com

17 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 Downloaded from www.pharmacy123.blogfa.com

18 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 Downloaded from www.pharmacy123.blogfa.com

19 Differential analysis of protein expression pH2pH12 Downloaded from www.pharmacy123.blogfa.com

20 Fluorescence-activated cell sorter Downloaded from www.pharmacy123.blogfa.com

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22 Sequencing I Downloaded from www.pharmacy123.blogfa.com

23 Sequen cing II. Downloaded from www.pharmacy123.blogfa.com

24 Sequencing III. Downloaded from www.pharmacy123.blogfa.com

25 RNA interference Downloaded from www.pharmacy123.blogfa.com

26 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) Downloaded from www.pharmacy123.blogfa.com

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28 Pedigree analysis T to A change in the  -globin gene – sickle cell anemia SS homozygous AS heterozygous (prenatal) AA homozygous Downloaded from www.pharmacy123.blogfa.com


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