Translational Elements (Copeland)

Question 1

eIF2

Answer 1

Step: Initation

Binds to: Initiator Met-tRNA

GTP?: Yes

Action:

• Delivers initiator tRNA to small ribo GTP hydrolysis releases eIF2 & signals for large ribo to bind
• *Phosphorylation of eIF2 INHIBITs translation in response to: Low aa concentration/poor nutrition; cellular stress; immune response; unfolded proteins

Question 2

eIF4E

Answer 2

Step: Initiation

Binds to: 5’ cap

GTP?: No

Action: Delivers mRNA to small ribo via 5’cap

Question 3

eIF4G

Answer 3

Step: Initation

Binds to: eIF4E

GTP?: NO

Action:

• Bridges/bends length between poly A tail & 5’cap
• Poliovirus (mRNA) binds directly to ribo without 5’cap direction, cleaves eIF4G - IRES binds to cleaved eIF4G & shifts to viral translation from host’s

Question 4

eEF1A

Answer 4

Step: Elongation

Binds to: tRNA

GTP?: Yes

Action:

• Binds aa-tRNA (except initiator & SC), delivers to A site
• GTP hydrolysis releases eIF1A & allows
• *peptide bond transfer P → A**

Question 5

eEF2

Answer 5

Step: Elongation

Binds to: A site

GTP?: Yes

Action:

• Catalyzes translocation of tRNAs in P & A → E & P; essential for translation
• GTP hydrolysis releases eF2 & A site free again
• Diptheria toxin inactivates EF2 and translation stops = toxic
  
  • • Fragment A = active, enters cytosol & catalyzes reaction to inactivate EF2
  • • Fragment B = toxin receptor ligand, allows it to enter cell

Question 6

eEFSec

Answer 6

Step: Elongation

Binds to: Sec-tRNA^Sec

GTP?: No

Action: Specialized elongation factor like eEF1A
Sec is essential for TH synthesis, so forms of hypothyroidisim caused by Sec-tRNASec specialized tRNA recognizing UGA codons

Question 7

eRF1

Answer 7

Step: Termination

Binds to: A site

GTP?: No

Action:

• Catalyzes release of the completed peptide at stop codon
• NOT a tRNA – no terminator tRNA

Question 8

SBP2

Answer 8

Step: Regulation

Binds to: SECIS element (3’ UTR insertion seq)

GTP?: No

Action:

• Assists getting eEFSec to ribo at UGA Sec codon
• Changes specificity from UGA-STOP to UGA-Sec

Question 9

miRNA

Answer 9

Step: Regulation

Binds to: mRNA (often 3’UTR)

GTP?: No

Action:

• Inhibit translation - RISC complex possibly physically impedes
• RNA-Induced Silencing Complex

Question 10

ApoB

Answer 10

Step: Regulation

Binds to: /

GTP?: No

Action:

• Enzymatically edited to short form for intestinal use (long in liver)
• Use deamination to make an early STOP

Question 11

IRP

Answer 11

Step: Regulation

Binds to: IRE

GTP?: No

Action:

• Maintains iron homeostasis
• Low Fe = IRP binds IRE and inhibits translation
• High Fe = IRP bound to Fe & can’t bind to IRE, translation proceeds

Question 12

eIF2B

Answer 12

Step: Regulation

Binds to:

• eIF2-GDP
• eIF2-GDP-P (higher affinity)

GTP?: indirect

Action:

• Recycles eIF2-GDP to eIF2-GTP as a GEF (guanine NT exchange factor)
• Ultimately helps assist in re-binding of GTP after hydrolysis, but when eIF2 is phosphorylated under stress conditions, it stably binds together, reducing effective eIF2B

Question 13

4EBP

Answer 13

Step: Regulation

Binds to: eIF4E

GTP?: No

Action:

• Inhibits translation by binding to eIF4E & preventing binding to the small ribo
• mTOR regulates 4EBP by phosphorylation (=inactivation) under non-hypoxic conditions Hypoxia inhibits mTOR = 4EBP dephosphorylation = decreased translation