Exam 3 - control of gene expression 2 Flashcards
What is negative and postive control of alternative splicing?
negative regulation of splicing is done by the repressor molecule and prevents splicing machinary from access to splice site
Postive regulation of splicing is done by the activating molecule and recruits and helps direct spling machinary. REQUIRED
What is the spatial localization of mRNA?
mRNA leaves nucleus through pores
- mRNAs traveling to destination use cytoskeletal motors
- Anchor proteins (black) hold mRNA in place
- Random movement
- Random mvoemnt + degeneration of RNA that is not trapped
What regulated rna stability?
Decapping of 5’ cap and degradation 3’ end of poly A tail .
3’ Poly A tail functions like a ticking time bomb and as exonuclase degrades more and more of it
What is an example of mRNA regulation ?
ex: control of RNA involved in iron metabolism
- Ferritin mRNA = storage of iron; ferritin protein binds to thousands of Fe and is intracellular
- stored in liver, lungs, pancreas
- TfR mRNA = iron absorbance
__________________________________________ - Iron starvation
- cells dont need to store iron
- decrease ferritin mRNA
- cell need to transport iron into cells
- increase transferrin receptor mRNA
- cells dont need to store iron
- Iron in Excess
- need to store excess iron
- Increase in ferritin mRNA
- since sastified they need less transport into cell
- decrease TfR mRNA
- need to store excess iron
- IRP = Iron Receptor Protein
- IRP binding to….. IRE (iron starvation)
- 5’ ferritin mRNA = NO FERRITIN MADE
- 3’ transferritin receptor mRNA = TfR PROTEIN MADE
- Excess iron - IRP binds to Fe
- produces more ferritin protein
- Reduces TfR protein
- IRP binding to….. IRE (iron starvation)
What is miRNA?
- non coding RNAs that silence expression of “specific” mRNA targets
- miRNAS bind to complementary sequences in the 3’ UT (untranslated region) end of mRNA
- degrade RNA or block translation
- life as a miRNA
- Created as primary miRNA w/ hair pin loop -> size is reduced and loop cleaved and then exported out nucleus -> premiRNA -> futhur cleaved by dicer enzyme -> form RISC (RNA induced silencing complex) futher interacts w/ miRNA ->mRNA base pairs mRNA -> cleaves RNA
- each miRNA can repress hundreds of mRNAs
- Both causitive and responsive
- Causitive = miRNAs likely have mutations that cause diease
- Responsive = increased miRNA expression = down regulation genes to limit severity
What is one example of causative diease nature of miRNA
Touretts syndrome
mutation in SLITRK1 MRNA -> increased miRNA binding
miRNA189 binds to 3’ UT on SLITRK1 mRNA decreases its expression. CHanges guanine to an Adenine on SLKRTK1
What are the ways in which a protein is processed and modified post transcriptionally
- fold into 3D structures
-
molecular chaperones assist in folding
- HSP (heat shock) heat protein to denature and facilitate proper refolding
- BInding of cofactors
- modifed by protein kinases
- glycoslated
- dimerization
- modifying enzymes to act on proteins
What is protein is responsible for protein degradation/
Proteasome
Degradation is ATP dependent
Cap binds to proteins selected for destruction and acts as a gate. activated on demand
How does degration occur via ubiquitin?
Ubiquitin removes unfolded or abnormal proteins
( the pictures explain everything )
1.) ubiquitin is attached to e1 via atp dependent reaction on the cys chain….
last step.) attached to protein is attached to lys as are the next ubiquitin tags
once proteosome recongizes tags then it is destoyed
specifity = 1 proteasome , 2 Et protein, 30 -40 e2, 600-700 e3
WHat is an example of proteasome and therapy?
The proteosome inhibtor called bortezomib is used to treat myelomas. Triggers apoptiosis in cancer cells by reversible inhibiting of protesome and allowing some pro apoptotic factors to work
myelomas - cancer of plasma cells .
abnormal cells accumulate in bone marrow, and interfere with RBC production
What are different ways to activate ubiquitin ligase ?
Phosphorlaytion by proten kinase and ATP
Allosteric transition via ligand
allosteric transition caused by protein subunit addition
What are other steps of activating of target proteins degradation signal
What are other ways to control for gene expression?
-
Coordinated expresion genes
- expression of critical regulatory proteins that can trigger battery of downstream genes. essential its coordinated
-
Decision for specialization
- combination of genes can produce many types of cells.
- regulatory proteins bound to DNA are inheirited
- ex: hematopoesis creation of myeloid lineage into RBC , megakaryocyte and WBC or lympoid lineage into T/B/NT cells
-
Methylation and genomic imprinting
- DNA can be regulated by proteins
- DNA it self is methlyated at 5’ carbon from cytosine to 5’ methylcytosine which shuts down expression of genes
- is inheirited and methylation is done by methyltransferase
- Genomic imprinting is expression of genetic material depending on parent of origin
- Epigenetics is regulation of expression in gene activity without altering gene structure (methylation)
-
X chromosome inactivation
- in females one X chromsome early in development one the x chromosmoes are condensed into heterochromatin which is called a barr body.
- inactivation is random where females are msoaics of 2 types of cells and either the paternal or maternal x is inactivated
3.
What is an example of a genomic imprinting disorder?
PRader willi Syndrome (PWS) - caused by paternal deletion on chromosme 15
pws inheirs gene deletion from father. Paternal gene expression means that even though the materal gene is correct you only express the paternal portion.
stage 1 = hyptonia
stage 2 = hyperphagia
Obesity is cardinal feature and most signific health probelm
hyperphagia
