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32 Cards in this Set

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What are TSF's regulated by what b/c of changes in TSF's?
Regulated in response to environmental factors
Signal transduction pathways result in changes in gene expression b/c of changes in TSF's
Describe the characteristics of DNA methylation
Some genes controlled this way
Assocoated with heritable gene inactivation
Required for X chromosome inactivation
Methylation usually occurs at a ceratin stage of development and/or tissues
Active promotors CANNOT by methylated and methylated promotors CANNOT be activated
Methyl C recruit chromatin and HDAC's to shut off tanscription completely
What are some important things about CpG islands?
C-G rich areas
Often at the 5' end of housekeeping genes which are normally not methylated
Inappropriate methylation of CpG islands in tummor suppresspr genes and/or genes encoing protein involved in apoptosis has been associated with some cancers
Alternative Sploicing and/or Polydenylation
Important for getting more then one protein from one mRNA
Major reason have few gens but many proteins
Constituitive Alternative Splicing
Not particulary regulated, not specific
Several version of a protein may be made in the same cell at the same time
Results from sequence at exon/intron borders dont conform prefectly to consensus makeing it more difficult for snRNP's to recognize
Regulated Alternative Splicing
More specific usually a tissue specific or developmental specific regulation
Addition or removal of a functional domain
Single cell will express only one version of teh protein at any given time
What are the different ways that alternative splicing can result in different proteins?
Optional Exon
Optional Intron
Mutually exclusive exons
Internal splice site
What are one of the ways you can regulate proteins?
Regulated the stability of mRNA which is sometimes faster that regulating at the transcritional level (no waiting for TSF's)
Describe the usual/defualt pathway for mRNA degradation
Shortening or removal of the poly A tail (deadenylation)
This leads to decay in 3' - 5' direction
Also can cause Decapping 5' end which can lead to decay
Decapping Pathway
Less common
Decapping starts first and you have degradation mostly from 5' end
Endonucleolytic Pathway
Less Common
Signal for endonuclease and lose PolA tail all at once whic triggers degradation for the 3' end
RNA Surveilance (nonsense)
Process by which aberrant transcripts (defective mRNA's)are rapidly degraded with out being deadenylated first
Can Detect: Early nonsense codons, unsplced intron and extended 3' UTR
What does the regulation of mRNA stability depnds on?
Depnds on sequeces in 3' UTR that increase or inhibit degradation
What happens when iron levels are low?
Endonucleolytic cleavage of mRNA is blocked which stabilizes the mRNA so more protein can be translated
What do both miRNA and siRNA do?
Both bind to target sites in the 3' UTR of target mRNA and inhibit protein synthesis
miRNA
Binds to sequences that are NOT compleatly complementary
One can regulate many mRNA's
If an mRNA has more then one are sequester in P bodies therefore not translated and eventually degraded
Important in cell growth and development
siRNA's
Bind to sequences that are perfectly complementary
Cause mRNA cleavage and rapid degradation
Protection of cell from viral infection
RNA editing
Rare mechanism to alter the sequence of mRNA after transcription
Editing of apolipoprotein B
Translation Regulation
Faster protein adjuestment then transcriptional
Short-term protein regulation
Important for developemtnal regulation
RBC's almost exclusively b/c no nucleus
Intiation is the rate limiting step and site of most regulation
Accessibility of 5' cap Initiation of Translation
Proteins that stabilize structures in the 5' UTR can repress translation by making the cap structure less accessible to cap-binding protein
Phosphorylation of eIF-2-GDP
Prevents formation of eIF-2-GTP
Overall inhibition of translational initiation and protein synthesis
What can 3' UTR sequeces do for mRNA?
Direct the mRNA to regions of the cell where translation is more or less likely to occur
Masking
Occurs during gametogensis
mRNA's sequestered and stored for later
3' UTR are required for unmasking
Two places protein can be synthesized
On "free" ribosomes in the cytosol
"Membranous"ribosomes bound to the ER
Proteins made on free ribosomes
Default=stay in cytosol
Signal for protein to go to mitochondria or nucleus
Post-Translational Tanslocation
Proteins made in the ER
Default = secretion
Co-translational translocation
Localization depends on signals provided by glycosylation patterns
Protein Folding
Occurs in ER lumen
Chaperones and Chaperonins
Mild folding varients can usually be controlled but those prone to aggregation can cause problems
Chaperone Proteins
Bind and stabilie unfolded or partially folded proteins
Preventing degradation ot aggregation
Chaperonin Proteins
Directly faciliate the folding of proteins
Proteasomes
Degrade most misfolded proteins
I-Cell Disease
Patients are unable to phosphoraylate the mannose.
Results in protein being secreted instead of localized
Proteasome
Degradation occurs
Found in cytosol
Contineous or regulated
Cell to be degraded must have Ubiquitin