Chapter 12: Regulation of Translation Flashcards
Translation rates respond to the () of the cell, reflected in the amount of amino acids present
nutritional state
In bacteria, () compete with charged tRNAs for binding at the A site
uncharged tRNAs
binding of uncharged tRNA in A site of bacterial ribosome results in recruitment of ()
RelA
RelA synthesizes lots of (p)ppGpp (a pentaphosphate guanine nucleotide called “()”) from GTP/GDP and ATP precursors.
magic spot
action of RelA modulates transcription and induces stress responses to replenish amino acids. This is called the “()”
stringent response
In eukaryotes, the uncharged tRNA binds to ();
Gcn2
When bound to tRNA, a kinase domain in Gcn2 phosphorylates the initiation factor () in euks.
eIF2
Phosphorylated eIF2 binds strongly to () (to the point where active eIF2 is effectively depleted from the cell), and cannot then be used for initiation, so translation is shut dow
eIF2B
Normally, eIF2 binds to eIF2B and exchanges ()
GDP for GTP
Phosphorylation at () results in constitutive binding of eIF2 to eIF2B, inhibiting translation initiation
serine 51 of the eIF2 alpha subunit
mRNAs compete for ()–this is another opportunity for translational regulation
translation machinery
eIF4E can be sequestered by a range of () in response to cellular conditions- this decreases overall translation activity
4E-BPs (eIF4E – Binding Proteins)
mRNAs assume () in different conditions–and these affect translation levels
different shapes
In bacteria,the Shine-Dalgarno sequence is often (), preventing translation initiation
obscured
() are another example-these small regulatory molecules control their own synthesis
Riboswitches
one riboswitch example is ()
thiamine synthesis
Another example of regulated SD sequestration mediated by protein: control of the expression of () in E.coli
threonine tRNA synthetase
5′UTR regulation is less common in eukaryotes, but is used for ()
iron regulation
Too much free iron is toxic, so iron is tightly bound to () (storage protein)–the higher the iron concentration, the more () is needed
ferritin
The 5′ UTR of ferritin mRNA has (1) that bind to (2)
- Iron Response Elements (IREs)
- Iron Regulatory Proteins (IRPs)
Gcn4 is a transcription activator of many amino acid synthesis genes -> its translation is activated by ()
cellular starvation
While eukaryotic 5’ UTR is relatively small in comparison to bacteria, eukaryotic () are large and regulation using these sequences is common, particularly in developmental regulation.
3′ UTRs
3’ UTRs can be the driving force in regulating gene expression in certain ().
developmental programs
In Xenopus laevis oocytes, maternally-derived mRNAs are not initially translated – they are ()
dormant, or translationally repressed
activation of translationally repressed mRNA in X. laevis depends on the ()
3’ UTR poly(A) tail length
The 3′ UTR cytoplasmic polyadenylation element (CPE) is bound by ().
CPEB
CPEB sequesters () via other proteins (i.e. Maskin), and this stops formation of the closed loop required for translation initiation
eIF4E
() is a type of 4E-BP that has additional specificity for CPEB.
Maskin
Dormant mRNAs are activated by phosphorylation of CPEB by kinase ().
Eg2
Phosphorylated CPEB recruits ().
CPSF (cytoplasmic polyadenylation specificity factor)
CPSF binds to standard AAUAAA polyadenylation signal and recruits () to the mRNA which eventually leads to the extension of the poly(A) tail
poly(A) polymerase (PAP)
() may also regulate translation in eukaryotes by binding partly complementary sequences in the 3ʹ UTR
microRNAs (miRNAs)
phosphorylation of eEF2 in response to stress leads to accumulation of () which inhibits elongation
pre-translocation-state ribosomes
Elongation regulation often accompanies () to help cells preserve and redirect limited resources under difficult conditions.
initiation regulation
Many of these battles between host and virus are fought in the initiation step ()
disrupting cap-dependent initiation
Picornaviruses (like polio) disrupt the formation of the host closed loop complex by ()
protein cleavage
Flu viruses disrupt closed-loop formation by ()
cleaving the 5′ cap
Encephalomyocarditis (another picornavirus)encodes proteins that (), leading to sequestering of eIF4E and disruption of initiation
dephosphorylate the 4E-BPs
Picornaviruses inhibit cap-dependent translation, so they themselves use cap-independent translation by using () within the 5′ UTR to directly recruit ribosomes
Internal Ribosome Entry Sites (IRES)
when binding to IRES (kind of analogous to Shine-Dalgarno) picornaviruses do not depend on eIF4 factors that it has destroyed, but rather utilizes ()
IRES-transacting factors (ITAFs)
Viruses can also simply compete for limited ()
translation factors
in euks., () phosphorylates eIF2 when activated by the presence of double-stranded viral RNA
PKR protein
In (): part of the 3′ UTR mimics tRNAVal, which then becomes acylated and initiates translation at an AUG, albeit with a mismatch
Turnip Yellow Mosaic Virus (TYMV)
In (): initiation is mediated by base-pairing between 3 nucleotides in the 5′ UTR (AGG) and 3 nucleotides right upstream of an alanine (CCU)
Cricket Paralysis Virus (CrPV)
