B2.053 Prework 2 Regulation of Protein Translation

Question 1

what are 2 mechanisms of translational regulation?

Answer 1

1. general factors (eIF) - broad/global

2. microRNA (miRNA) - specific

Question 2

what is the endoplasmic reticulum stress response?

Answer 2

secreted/cell surface proteins are synthesized in ER

stress conditions: proteins fold incorrectly, accumulate in the ER

Question 3

what types of stressers contribute to ER stress?

Answer 3

calcium depletion
reduction of disulfide bonds
expression of mutant proteins
ischemia
UV light exposure

Question 4

what are the 4 kinases that can phosphorylate eIF2a and inhibit translation?

Answer 4

1. PKR - activated by viral dsRNA
2. GCN5 - activated by low amino acids/ glucose (nutritional stress)
3. HRI - activated by low heme only in immature erythrocytes
4. PERK - activated by ER stress/unfolded proteins

Question 5

describe the pathway by which PERK shuts down transcription

Answer 5

PERK kinase activated
PERK phosphorylates eIF2a
phosphor-eIF2a cannot participate in initiation

Question 6

what are the two outcomes of eIF2a phosphorylation?

Answer 6

1. most protein translation stops

2. transcription of specific mRNAs into protein increases

Question 7

what transcription factor is activated with P-eIF2a?

Answer 7

ATF4
upregulates pro recovery mechanisms
Proteases
Chaperones
Anti-oxidants

Question 8

what protein activated by ATF4 leads to apoptosis?

Answer 8

CHOP

over time, builds up to sufficient amount to stimulate apoptosis

Question 9

what is the function of 4E binding proteins?

Answer 9

bind/sequester eIF4E

release eIF4E when phosphorylated

Question 10

how does insulin influence 4E BPs?

Answer 10

insulin stimulates a kinase cascade that phosphorylates 4E-BP and releases eIF4E to increase translation

Question 11

what are micro RNAs?

Answer 11

21/22 nucleotide RNAs
coded for by specific genes
processed from longer RNA transcripts
repress translation and cause mRNA degradation

Question 12

were do miRNAs bind to mRNAs?

Answer 12

3’UTR

UTR=untranslated region

Question 13

what is the structure of miRNAs?

Answer 13

hairpin structure with intramolecular base pairing

Question 14

what protein complex is associated with miRNAs?

Answer 14

RNA-induced silencing complex, RISC

Question 15

what is the difference between the effects of siRNAs and miRNAs?

Answer 15

siRNAs induce mRNA degradation

miRNA decrease translation and induce mRNA degradation

Question 16

discuss the potential therapeutic application of miRNAs

Answer 16

potential therapeutic approach: silence expression of protein required for pathology
dsRNA oligonucleotides delivered as "drug"
called RNAi (RNA interference)

Question 17

what is the function of about 1/2 of antibiotics?

Answer 17

inhibit bacterial translation to kill the bacteria

Question 18

what is important about using translation inhibitor antibiotics?

Answer 18

they inhibit the synthesis of bacterial toxins even before the bacteria itself is killed

Question 19

what is an example of a bacterial translation inhibitor?

Answer 19

aminoglycosides (streptomycin)

bind to 30S subunit of bacterial ribosome

Question 20

what are 3 mechanisms by which aminoglycosides can inhibit translation?

Answer 20

block initiation
block further translation and elicits premature termination
incorporation of incorrect amino acid