Flashcards in B2.053 Prework 2 Regulation of Protein Translation Deck (20)
what are 2 mechanisms of translational regulation?
1. general factors (eIF) - broad/global
2. microRNA (miRNA) - specific
what is the endoplasmic reticulum stress response?
secreted/cell surface proteins are synthesized in ER
stress conditions: proteins fold incorrectly, accumulate in the ER
what types of stressers contribute to ER stress?
reduction of disulfide bonds
expression of mutant proteins
UV light exposure
what are the 4 kinases that can phosphorylate eIF2a and inhibit translation?
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
describe the pathway by which PERK shuts down transcription
PERK kinase activated
PERK phosphorylates eIF2a
phosphor-eIF2a cannot participate in initiation
what are the two outcomes of eIF2a phosphorylation?
1. most protein translation stops
2. transcription of specific mRNAs into protein increases
what transcription factor is activated with P-eIF2a?
upregulates pro recovery mechanisms
what protein activated by ATF4 leads to apoptosis?
over time, builds up to sufficient amount to stimulate apoptosis
what is the function of 4E binding proteins?
release eIF4E when phosphorylated
how does insulin influence 4E BPs?
insulin stimulates a kinase cascade that phosphorylates 4E-BP and releases eIF4E to increase translation
what are micro RNAs?
21/22 nucleotide RNAs
coded for by specific genes
processed from longer RNA transcripts
repress translation and cause mRNA degradation
were do miRNAs bind to mRNAs?
what is the structure of miRNAs?
hairpin structure with intramolecular base pairing
what protein complex is associated with miRNAs?
RNA-induced silencing complex, RISC
what is the difference between the effects of siRNAs and miRNAs?
siRNAs induce mRNA degradation
miRNA decrease translation and induce mRNA degradation
discuss the potential therapeutic application of miRNAs
potential therapeutic approach: silence expression of protein required for pathology
dsRNA oligonucleotides delivered as "drug"
called RNAi (RNA interference)
what is the function of about 1/2 of antibiotics?
inhibit bacterial translation to kill the bacteria
what is important about using translation inhibitor antibiotics?
they inhibit the synthesis of bacterial toxins even before the bacteria itself is killed
what is an example of a bacterial translation inhibitor?
bind to 30S subunit of bacterial ribosome