Lecture 7: Regulation of the Proteome Flashcards
(19 cards)
Describe the prokaryotic translational start sequence
Shine Dalgarno (SD) sequence, upstream of AUG start codon
NEEDED to correctly position AUG in the ribosome and provide translational control
What are the four mechanisms of translational regulation in prokaryotes
1) Specific RNA binding protein blocks access to the SD sequence
2) temperature-regulated stem-loop RNA structures block access to the SD and are broken down in high temperatures to expose SD for binding
3) A small molecule called a riboswitch binds and causes structural rearrangement of RNA, blocking SD
4) Antisense RNA tat is produced elsewhere in the genome base-pairs with mRNA and blocks the SD
Explain ferritin translation under low vs high iron conditions
low iron conditions: aconitase binds to ferritin near start site and blocks translation of ferritin protein
high iron conditions: iron binds to aconitase, resulting in a conformational change that releases ferritin mRNA. Ferritin protein is translated
What is ferritin and when is it needed
ferritin binds iron when it is high and releases it slowly to avoid toxicity
What is transferrin and when is it needed
imports iron into the cell and is needed when iron is low
Explain transferrin translation under low vs high iron conditions
low iron conditions: aconitase binds to 3’UTR and stabalizes mRNA allowing transferrin to be translated
high iron conditions: iron binds to aconitase, causing a conformational change that releases it from mRNA . This exposes the 5’UTR endonucleic clevage site, poly A tail is removed and mRNA is degraded
Repressor proteins
can interfere with 5’ cap and polyA tail intreactions needed for efficient translation
miRNAs
can regulate eukaryotic translation
What is the most important eukaryotic initiation factor
eIF2
Describe how eIF2 initiates translation
1) eIF2 forms a complex with GTP
2) eIF2-GTP recruits the initiator tRNA to the small ribosomal subunit
3) Small ribosomal subunit binds the 5’ end of mRNA and scans for the first AUG
Describe how eIF2 deactivates
1) AUG recognized
2) eIF2 hydrolyzes GTP to GDP
3) THis causes a conformational change and eIF2 bound to GDP is released and inactive
How is eIF2 reactivated to start another round of translation
requires eIF2B, a guanine nucleotide exchange factor (GEF), which exchanges the GDP for GTP
Why is it necessary for eIF2 reactivation to be controlled
for when there is a low nutrient environment, no amino acids, or too much protein has been made already. Cell wants to slow protein synthesis
How is eIF2 reactivation controlled
specific protein kinases phosphorylate eIF2. it is still GDP-bound and inactive.
eIF2B binds to the phosphorylated eIF2 but is unable to activate eIF2
Since there is much more eIF2 than eIF2B, phosphorylation of a few eIF2s leaves ALL eIF2B stuck (sequestered)
How can translation be restarted after it is slowed
remove phosphate group from eIF2
Are all mRNAs equally effected by eIF2 phosphorylations
NO. key RNAs can bypass because slowing protein translation of proteins needed for cell function/life would be bad
What are chaperones and what are many of them called? two examples.
proteins that help ither proteins fold. Many are called heat-shock proteins because they are synthesized to high amounts by cells at high temperatures.
Hsp70 and Hsp 60
Describe the action of Hsp 60 and Hsp 70
Hsp 70 helps folding upon exiting ribosomes by sticking to hydrophobic regions and using ATP
If protein is still not folded properly, travels to Hsp60, a double-barreled “isolation chamber” that takes in protein, covers witth GroES cap and uses ATP to help fold properly
What happens if proteins are not folded properly
can aggregate and become toxic to cells
This is closely monitored by the proteosomes, which can degrade misfolded proteins
