Lecture 10 Control Of Gene Expression 2 Flashcards
1
Q
Alternative splicing produces
A
Different forms of proteins form the same gene
2
Q
RNA splicing can be regulated negatively by______ that prevent splicing machinery access to splice site
A
Repress or molecule
3
Q
RNA splicing can be regulated positively by ______ that recruits and helps direct splicing machinery
A
Activating molecule
4
Q
mRNAs leave nucleus through
A
Pores
5
Q
After mRNAs leave nucleus through pores they travel to
A
Destination using cytoskeletal motors (anchor proteins hold them in place)
6
Q
If mRNA is not anchored in the cytoskeleton it
A
Gets degraded
7
Q
miRNA involvement was found in 1 form of Tourette’s syndrome. The variant in what gene is associated to this 1 form
A
SLITRK1 (change on target mRNA leads to increased mRNA binding)
8
Q
___% of genes in humans undergo alternative RNA processing
A
75%
9
Q
Intracellular protein, that binds to thousands of Fe3+/molecule, and is found in most cells
A
ferritin
10
Q
Granules of ferritin
A
Hemosiderin
11
Q
Excess iron is mainly stored by
A
- liver
- lungs
- pancreas
12
Q
During iron starvation
A
- cells do not need to store iron
- decrease ferritin mRNA(encodes storage protein)
- Cells must transport iron into cells
- Make more transferrin receptor (TfR) mRNA
13
Q
Iron in excess
A
- need to store excess iron
- make more ferritin mRNA (makes storage protein)
- and transport less iron into cell
- Make less TfR mRNA (makes Fe transport protein)
14
Q
mRNA regulation of iron transport involves _____ and _____
A
Iron responsive elements (IREs) and Iron responsive regulatory protein (IRP)- aconitase
15
Q
When Iron responsive protein binds to Iron responsive elements at the 5’ ferritin mRNA there is
A
no ferritin made
16
Q
When Iron responsive protein binds to Iron responsive elements at 3’ transferrin receptor mRNA there is
A
transferrin receptor made
17
Q
____ are regulatory RNAs that regulate messenger RNAs
A
microRNAs
18
Q
microRNAs are ____ RNAs; ____ nucleotides long- that silence expression of specific mRNA targets
A
noncoding, 22
19
Q
microRNAs bind to complementary sequences in the _____ end of mRNA
A
3’ UT
20
Q
microRNAs _____ RNA or _____ translation
A
degrade, block
21
Q
microRNAs are ____ of gene activity
A
repressors
22
Q
microRNAs originate as ____ nucleotide precursors
A
100
23
Q
MicroRNAs is made as a primary miRNA: pri-miRNA- RNA with _____ then it is cut down in size to ______ and then further processed to mature miRNA
A
RNA with hairpin loop, pre-miRNA
24
Q
Precursor miRNA is ____ in the nucleus and forms a ______ structure it is then further cleaved by ____ enzyme and joins with ___ and other proteins to form __________
A
cropped in the nucleus and forms a double stranded loop structure, Dicer, joins with Argonaute and other proteins to form RISC: RNA-inducing silencing complex
25
RNA-inducing silencing complex base pairs with ____
mRNA
26
After RISC (RNA-induced silencing complex base pairs with mRNA) base pairs with mRNA it cleaves ____ and _____
RNA (note that this requires ATP) and shuts down expression
27
there are more than _____ miRNAs in the human genome
5,600
28
miRNAs occur in ___ in genome
clusters
29
Can a miRNA regulate more than 1 mRNA
yes
30
each miRNA can repress ______ of mRNAs
hundreds
31
miRNAs may target __% of mammalian genes
60%
32
miRNA binding sites are _____
widespread
33
Can 1 miRNA effect a whole biological program
yes
34
miRNAs change their expression profile in _____ states
disease (for example certain miRNAs can be elevated in stroke or cardiovascular disease)
35
can circulating levels of miRNAs can be used to identify cancer
Yes
36
miRNA-____ serum levels are elevated in prostate cancer
141
37
miRNA-____ decreased in expression of heart disease
29
38
Can miRNA serve as a biomarker
yes
39
Are changes in microRNA expression the cause of disease or response
- both
- miRNAs likely have mutations that cause disease
- increased miRNA expression down regulates genes in response to disease to limit severity
40
Neurological disorder manifested by motor and vocal tics
Tourette's syndrome
41
Tourette's syndrome affects as many as ___ in ____ individuals
1 in 100
42
miRNA involvement was found with ___ form of Tourette's syndrome. what is/are the variant(s)
1, Variant of SLITRK1 gene shown associated with Tourette's syndrome, A change in recognition sequence on target SLITRK1 mRNA increases miRNA binding
43
change in recognition sequence on target SLITRK1 mRNA leads to
increased miRNA binding (thus leading to Tourette's Syndrome)
44
miR-___ binds more efficiently to target sequence in 3'UT of SLITRK1 gene and decreases SLITRK1 expression thus leading to Tourette's syndrome
189
45
Post translational modifications are require by proteins to be
functional
46
proteins must fold into _____ conformations
3-D
47
______ help proteins fold appropriately
molecular chaperones
48
examples of post transcriptional modifications required proteins to be funcitonal
- proteins must fold into 3-D conformations
- molecular chaperones help proteins fold appropriately
- Bind co-factors
- Modified by protein kinases
- Glycosylated
- bind to other protein subunits or protein partners
- modifying enzymes act on protein
49
What is an example of modifying enzymes acting on protein
Thrombin cuts fibrinogen to form fibrin in blood clotting
50
Many molecular chaperones are _______ synthesized in dramatic amounts when temperature is raised (37 degrees C to 42 degrees C)
Heat shock proteins (Hsp)
51
why are heat shock proteins needed
- increase in temperature leads to increase in misfiling of proteins
- There is feedback to synthesize chaperones (Hsp) to help proteins refold
52
What are the two major families of heat shock proteins
HSP60 and Hsp70 (70kDa)
53
proteins can be regulated by degradation by the ______
proteasome
54
Hollow chamber where proteins are degraded
Proteasome
55
The Proteasome has ____ active sites that are ____ dependent
6, ATP
56
The cap area ___ to proteins selected for destruction it then acts as a ____ for proteasome
binds, gate
57
What is the recognition tag to help proteasome identify proteins for degradation
Ubiquitin
58
ubiquitin is about ____ amino acids
76
59
____ ubiquitin activating enzyme involved in first step of marking protein for degradation
E1
60
The first step of marking a marking of proteins by ubiquitin C-terminus of ubiquitin is initially activated by being linked via a high-energy thioester bond to the _____ side chain on the ____
Cysteine, E1 protein
61
The second step of marking a protein with ubiquitin is the ubiquitin is transferred to
E2 ubiquitin ligase (with accessory protein E3)
62
after the ubiquitin is transferred to E2 ubiquitin ligase (with accessory protein E3) the complex is now
primed to mark proteins for destruction
63
Ubiquitin removes
unfolded or abnormal proteins
64
Addition of ______ (with degradation signal) to ubiquitin ligase primed with ubiquitin. And the first ubiquitin chain is added to _____ side chain on protein
protein, lysine
65
after the addition of the first ubiquitin each successive ubiquitin added to ____ of ubiquitin chain by ______
lysine side chain of ubiquitin chain by E1 enzymes
66
Targeted ubiquitin chain on target protein is recognized by ____
proteosome
67
Apparatus that deliberately destroys aberrant protein
Proteasome
68
in humans their are ____ E1 ubiquitin activating enzymes
two
69
In humans their are ____ type of proteasome
1
70
In humans there are ____ types of E2 ubiquitin conjugating enzymes and ____ of E3 accessory proteins
30-40 and 600-750
71
Proteasome inhibitors are used to treat
multiple myelomas
72
Cancer of plasma cells
myelomas
73
Myelomas leads to abnormal cells accumulating in bone marrow and this interferes with ____ production leading to _____
RBC production leading to anemia
74
Multiple myelomas are incurable but
treatable
75
What is the drug name for an inhibitor of proteasome that is highly effective in treating multiple myeloma
Bortezomib
76
what was the first patient treated with Bortezomib
pt007 JB
77
The chamber in proteasome has ___ proteolytic sites
3
78
Bortezomid interacts with ___ proteolytic sites in proteasome
1
79
Ubiquitin ligase is activated by
- phosphorylation by protein kinase
- allosteric transition caused by ligand binding
- allosteric transition caused by protein subunit addition
80
ways the target protein degradation signal can be activated
- phosphorylation by protein kinase
- Unmasking by protein dissociation
- creation of destabilizing N-terminus
81
Other controls of gene expression
- coordinated expression of genes: genes do not exist in a vacuum
- Decision for specialization: what kind of cell do I want to become
- methylation and genomic imprinting: what genes get expressed (or not) from Mom and Dad
- X-chromosome inactivation: even things out XX vs. XY- 2 X chromosomes vs. 1 X chromosome
82
What is coordinated gene expression
- expression of critical regulatory protein can trigger batter of downstream genes
- coordinated gene expression in response to need
83
What is an example of coordinated gene expression
Glucocorticoid cortisol- response to stress- increase blood sugar- aid in fat, protein, carbohydrate metabolism (hiest at 8am and lowest at midnight)
84
Explain decision for specialization
- combinations of gene control can produce many types of cells
- Decision at each step
- result is several different cell types
85
what is an example of decision of specialization
Hematopoiesis (HSC becomes HPC that can then become lymphoid lineage or myeloid lineage)
86
what is the effect of DNA methylation on gene expression
it represses gene expression
87
Can we inherit DNA methylation
yes
88
Cytosine is methylated by _____
maintenance methyltransferase
89
DNA methylation of the parent strand
serves as a template for daughter strand
90
Genomic imprinting is based on ______
DNA methylation
91
what is genomic imprinting
- differential expression of genetic material depending on the parent origin
- expression of some genes depends on whether genes inherited from mother or father
92
Regulation of expression of gene activity without altering gene structure
Epigenetics
93
What is an example of epigenetics
methylation
94
Caused by paternal deletion on chromosome 15 in the region of 15q11-q13 (paternal genes expressed) while the maternal is silenced
Prader Willi (PWS) syndrome
95
Prader Willi syndrome (PWS) subjects inherit gene deletion from
father (note the deletion is on chromosome 15)
96
Stage one of Prader Willi (PWS) syndrome
Infantile hypotonia; poor suck; feeding difficulties- failure to thrive
97
Stage two Prader Willi syndrome (PWS)
Hyperphagia (uncontrollable eating); onset of early childhood obesity
98
____ is a cardinal feature of Prader-Willi syndrome (PWS) and most significant health problem
Obesity
99
What is the major cause of obesity in order will syndrome (PWS)
Hyperphagia
100
What is the average age of onset for Prader Willi obesity ___ years ; range _____ years may occur as early as ___ months
2 years, range 1-6 years may occur as early as 6 months
101
Prader-willi syndrome may lead to greater than ___% body fat, or ____ times higher than in the general population
40%, or 2-3 times higher
102
What are the symptoms of Prader-Wlli syndrome
- obesity
- Hypogonadism
- short stature; small hands and feet
- hypopigmentation
- mental deficiency; behavioral problems (skin picking, obsessive compulsive disorder)
103
What causes Prader Willi syndrome (PWS)
Paternal 15q11-q13 deletion: inherit deletion on chromosome 15 from Dad while maternal genes are not expressed (even though they are normal) this is due to genomic imprinting
104
____ occurs so equal number of genes expressed from X chromosome is equal in males and females
dosage compensation
105
The inactivation of one X chromosome in females occurs _____, The inactive chromosome becomes very highly condensed forming a ____. This inactivation is ____
early in development, Barr body, random
106
Why are females mosaics of 2 types of cells
either the paternal X or maternal X is inactivated
107
Inactivation of X chromosome is maintained post cell divisions. reprogramming of X chromosomes occurs during
gamete cell formation
108
The ______ is where inactivation of X chromosome start and spreads
X-inactivation center (XIC)
109
The X-inactivation center (XIC) makes _____ RNA that coats entire X chromsome
XIST RNA
