Lecture 27

Question 1

Cytoplasmic Polyadenylation and regulaiton for embryogenesis

Answer 1

mRNAs required for initial stages of embryogenesis are transcribed during oogenesis and stored in the egg.

To prevent early development the mRNAs must be silenced

SO 3’UTR and poly(A) tail

Question 2

Translational Dormancy for PolyA

Answer 2

CPEB binds CPE then recruits Maskin and binds eIF4E and prevents further binding of eIF4G so no recruit of 40S

Question 3

Translation of egg mRNA after fertilization

Answer 3

CPEB is phosphorylated thus releases Maskin allowing recruitment of eIF4

CPSF and PAP bind mRNA and lengthen tail

PABPC1 and 2 then bind eIF4G to the tail enabling ribosomal recruitment

Question 4

Learning and Memory

Answer 4

Protein synthesis from mRNAs stored in the post-synaptic neuron by synaptic activity leading to phosphorylation of CPEB

Question 5

Drosophila Translational Control

Answer 5

Hunchback and Nanos
useful for anterior and posterior patterning

d4EHP(binds cap) and Nos/Pum/Brat tether hb mRNA to inactive form

Question 6

Ferritin

Answer 6

Aconite must be in active form when iron is low to allow for no translation initiation

Question 7

Global regulation of translation

Answer 7

TOR pathway regulates cell growth and proliferation by integrating input from nutrient sensors

Inactivates 4EBP (competitive inhibitor of eIF4G

Activates ribosomal proteins S6 kinase

Question 8

Global regulation of translation by eIF2 kinases

Answer 8

• eIF2 brings Met-tRNAito the P site on the small ribosomal subunit. Only eIF2-GTP can do that. When the initiation codon is reached, eIF2-GTP gets hydrolyzed to eIF2-GDP and is released. This ensures that only a small ribosomal subunit with a properly bound initiator tRNA can associate with the large ribosomal subunit.
• Phosphorylation of eIF2 greatly increases its affinity for its GEF, which blocks its recycling and prevents most eIF2-GDP from getting converted to eIF2-GTP. This inhibits nearly all protein synthesis.

Question 9

Human cells have four eIF2 kinases that are activated by types of cellular stress

Answer 9

*GCN2 is activated by binding uncharged tRNAs. Uncharged tRNAs accumulate when amino acid levels are low.
*PEK is activated by misfolded proteins.
*Heme-regulated inhibitor (HRI) is activated in red blood cells when heme concentration is too low, and in other cells during oxidative stress or heat shock.
*PKR is activated by double-stranded RNA, which normally is only produced during viral infection.