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Last Class: Gene Regulation 1

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Presentation on theme: "Last Class: Gene Regulation 1"— Presentation transcript:

1 Last Class: Gene Regulation 1
Last Class: Gene Regulation 1. DNA-protein interaction, different motifs, techniques to study DNA-protein interaction 2. Gene regulation on DNAs, gene activators (acting on promoter, enhancer, chromatin etc), repressors 3. regulation of gene activators/repressors 4. integrated response.

2 Posttranscriptional Regulations

3 Posttranscriptional regulation possibilities

4 Alternative RNA Splicing

5 Alternative Splicing of RNA of the Drosophila DSCAM gene (axon guidance receptors directing growth cone localization)

6 Negative and Positive Controls of Alternative Splicing (active regulation) sometimes, the splicing sequence is ambiguous, so constitutive random splicing

7 Antibodies (membrane-bound, secreted) in B lymphocyte cleavage regulated RNA processing (CstF)

8 RNA Editing (inserting Uracil at different sites and change encoding sequence)

9 Nuclear Export Rev binds to rev response elelent (RRE), which binds to nuclear export receptor (exportin 1) to regulate nuclear export even without splicing a delay of virus infection symptom

10 Localization in cytoplasm also determine the fate of RNAs 3’ UTR (untranslated region)

11 3’ UTR in regulating Localization Red: intact 3’ UTR, Green: 3’ UTR deleted

12 Translational Regulation

13 Negative Translational Control aconitase inhibits ferritin production

14 Phosphorylation Regulation eIF-2B serving as GEF for eIF-2 and promote translation initiation phosphorylation locked eIF-2 in inactive form

15 Internal Ribosome Entry Site (IRES)

16 Two Mechanisms of mRNA decay 1
Two Mechanisms of mRNA decay 1. regular 3’ tail shortening followed by ‘5 decapping and degradation 2. endonucleolytic cleavage and fast decapping and degrading

17 The competition between mRNA translation and decay initiation machinery and deadenylation proteins are all associated with 5’ and 3’

18 With Iron, aconitase release enhances the production of ferritin to bind iron while destabilizes transferrin receptor mRNA to reduce the transportation of more iron intracellularly

19 Stop Codon Checking Should after all the exons (nonsense-mediated mRNA decaying)

20 SiRNA Mechanism RNase, ATP hydrolysis and RNA helicase

21 Summary Premature termination Alternative RNA Splicing
3’ cleavage and Poly A’ addition RNA editing Necleus transportation Localization of RNA at the cytoplasm Translational initiation Degradation

22 Cell Membranes Lipid Bilayers Cell Membrane

23 Cell Membrane Views

24 Phospholipid Molecule

25 Hydrophilic and Hydrophobic Molecules interacting differently with water

26 Wedge-shaped lipids form micelles
Cylinder-shaped lipids form bilayers

27 Spontaneous sealing of phospholipid bilayer

28 Proved the self sealing process
Liposomes Proved the self sealing process

29 Phospholipid mobility
Lateral diffusion: Diffusion coefficient 10-8 cm2/sec Migrate in seconds to cover the whole surface Flip-Flop: phospholipid translocators

30 Cis-double bonds affect packing
Saturated: packed and thick Unsaturated : loose and think Phase transition: liquid to fluid

31 Cholesterol and Glycolipids

32 Function of Cholesterol
Provide structural support, prevent small molecule to pass Prevent tight packing and transition

33

34 Phospholipid types

35 Microdomains on plasma membrane
Lipid rafts (~ 50nm) Choresterol Sphingolipids (long saturated chains) Other proteins

36 Asymmetrical distribution of phospholipids and glycolipids
Protein kinase C (PKC) binds to negatively charged phosphotidylserine to be functional

37 GEF, AKT, migrating front
Phospholipids in cell signaling PKC Calcium GEF, AKT, migrating front

38 Phospholipase Cleavage sites

39 Phosphotidylserine exposed on outer surface as apoptosis signal
Phospholipid translocator Scramblase

40 Glycolipids Gm1 Ganglioside with charge can serve as signal for lipid rafts, binds to Cholera toxin

41 Summary Lipid molecules: phospholipids, cholesterol, glycolipid, all amphipathic Lipid bilayer, hydrophobic inside and hydrophilic outside Subdomains on membrane, asymmetry important for functions Phospholipids as signals

42 Membrane Proteins Integral membrane protein
Peripheral membrane protein Glycosylphosphatidylinositol (GPI) anchor protein

43 Fatty acid chain (acyl, N-terminal) or prenyl group modifications (C-terminal)
Or palmitic acid Or geranylgeranyl

44 Index of hydrophobicity
Hydropathy Plots Index of hydrophobicity

45 Membrane proteins are glycosylated
Sugar are added in the lumen of the ER and Golgi apparatus, therefore, sugar are outside of cell surface Cytosol has reduced environment, preventing disulfide bonds


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