II. Post-transcription | 25B. Initiation of the translation in pro- and eukaryotes; regulation of eukaryotic translation; the role of phosphorylation of eIF2α

Question 1

1. Why is translation regulated?

Answer 1

It has to be regulated because non-wanted protein may causes diseases like cancer

Question 2

2. Regulation of eukaryotic translation
   a/ What are the 5 types of eukaryotic translation regulations?

Answer 2

1. RNA quality control
2. Regulation by microRNA
3. Regulation by the hairpin structure
4. Regulation by IRES
5. Regulation by modification of the IFs

Question 3

2. Regulation of eukaryotic translation
   b/ How does RNA quality control participate in regulation of eukaryotic translation

Answer 3

Upf triggers mRNA degradation (RNA quality control)
- During normal splicing, when the 2 exons are joining together- creating an exon junction complexes which is a protein complex (protein that dedicated to recognize the joining of these 2 exons).
- During the translation, when the ribosome coming along it push down the EJCs from the mRNA and then it reaches to the stop codon.
- During abnormal splicing, one of the introns didn’t spliced. During the translation, when the ribosome coming along and it gets to the stop codon which is part of the intron, there behind the stop codon EJC left (in normal situation there is no EJC downstream). The ribosomal subunits with join together with the EJC –> signal for degradation for the RNA
=> this way, during the ribosome check to mRNA whether the splicing went well.

Question 4

2. Regulation of eukaryotic translation
   c/ How does Regulation by micro RNA participate in regulation of eukaryotic translation

Answer 4

RNA interference
i) Double stranded RNA is cleaved by dicer into siRNA and miRNA
ii) These two bind with the RISC complex to degrade mRNA
iii) Resulting in no protein production

Question 5

2. Regulation of eukaryotic translation
   d/ How does Regulation by the hairpin structure participate in regulation of eukaryotic translation

Answer 5

Question 6

2. Regulation of eukaryotic translation
   e/ How does Regulation by IRES participate in regulation of eukaryotic translation

Answer 6

• IRES (internal ribosomal entry site) is a complex found at the 5’ end in case of no 5’ cap
• Ensures translation mechanism during apoptosis and mitosis.

Question 7

2. Regulation of eukaryotic translation
   f/ How does Regulation by modification of the IFs participate in regulation of eukaryotic translation

Answer 7

Protein synthesis control point – phosphorylation of eIF2α

Question 8

3. What is the role of eIF2α phosphorylation?

Answer 8

• Ternary complex only forms when eIF2 associates with GTP, and tRNAiMet will only be bound when GTP associates with eIF2
• When the cell is under stress, phosphorylation of the α- subunit of the eIF inhibits translation initiation
• The phosphorylated complex cannot exchange the bound GDP for GTP – since eIF2 cannot bind tRNAiMet -> no protein synthesis will occur

***tRNAiMet (initiator methionyl-tRNA)