Concepts in Molecular Biology
University of Vienna
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Proteolytic Degradation
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---20December 20222022/2023
- 	How do vertebrates form and function with only 20.000 protein-coding genes? 
 
We need to increase the number of functional proteins and entities that we have in the cell, in part this is done by differential splicing. Most transcription genes in mamalians system get spliced into 5 different variants, increasing it by 5. Other things, is to also add a dynamic to this because we are also changing environments and we need to deal with this. 
So we need do adap to different enviroments and enti...
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Translation and protein folding
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---8December 20222022/2023
- PROTEIN TARGETING 
Almost all proteins in eukaryotic cells are made in the cytoplasm, but they need to go to a cerintain place to function such as membrane, mithocondria, golgi apparatus, nucleus… 
 
Membrane proteins need something that make them bind to the membrane, and they can be integral membrane proteins, and outer member proteins. 
Transmember proteins, and peritheral membrane proteins what interact with one side of the membrane but are not fully integrated. 
 
Targeting of membr...
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RNA processing | part 2
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---9December 20222022/2023
- We have preveuosly discussed how the pre-mRNA is capped and the nuclear cap binding complex CBC is deposited; we have splicing, introns are rmoved; there’s a specific complex deposited in mammalian cells, called the exon-junctions complex EJC that is deposited upstream of these exons-exons junctions. 
Furthermore, at the 3’ end most mRNA are poly-adenylated having a poly-A tail that can be between 80 – 250 As long; this is then also bind by the poly A binding protein PABPN1. 
All the thre...
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RNA processing
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---8December 20222022/2023
- There are many different RNA molecules inside a cell: double stranded rna, circular rna, nuclear rna, rRra, micro rna, messenger rna… etc. 
 
Rna is heavily processed, it means that POL II transcribes rna but then it goes under other processes such es the splicing, the 5’ capping, the poly-adenylation, and editing such as base insertions, deletion, modification. 
 
What is the challenge for the cell? 
why are there so many modifications? 
why do most RNA processing reactions happen co-trans...
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Transcription and Regulation: 3D genome organization, loop extrusion, enhancer promoter communication
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---10December 20222022/2023
- -	Forced interaction between enhancer and promoter leads to activation. 
-	Deletion or inversion of TAD boundaries can affect gene expression. 
-	But TAD organization might only be one puzzle piece since completely disrupting TAD organization has minor effects on gene expression. 
-	Similarly: loss of cohesion or CTCF has minor effects on gene expression 
-	Enhancers and promoters come into proximity, but how close is close enough? 
-	With increasing distance between enhancer and promoter addi...
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Transcription and Regulation: Epigenetics, histone modifications
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---9December 20222022/2023
- -	While methylation of histone tails has dedicated and substrate specific enzymes doing their job, acetylation can be carried out by a family of multifunctional enzymes 
-	H3K27ac is a very useful mark for active chromatin and can predict enhancer activity and thereby gene expression 
-	But function of the individual mark (unlike H3K9me3 or H3K27me3) is unclear, might be part of a multivalent interaction landscape 
-	Loss of K27me3 might be more important then loss of K27ac
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RNA polimerase
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---9December 20222022/2023
- -	The unstructured domain of Pol II is important for its function and regulation 
-	Too short or too long is detrimental 
-	The CTD can carry a wide range of post-translational modifications 
-	Modifications can be recognized by specific proteins (=readers) 
-	Modifications change the biophysical properties of the CTD
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