(69)
19. Give et eksempel på hvordan translationsprocessen kan reguleres
Devlin, s.271-2
 

The most common and effective mechanisms for regulation are at the initiation stage.  
 

One of the most used examples of the translation regulation is posttranscriptional changes of mRNA, involving aconitase binding to specific non-coding sequences of the mRNA, called iron-responsive elements.

There are three proteins in our body that are important for the iron level. The first one, called transferrin, binds iron in the digestive system and transports it through the serum. The second one, the transferrin binding receptor, takes up iron from the extracellular fluid into the cell. The third one, called apoferritin, stores the iron in the cells.

(obs! Transferrin and transferrin binding receptor are regarded to be the same in this example)
 

We take a look at two situations: too little and too much iron in the cells in connection with both transferrin and apoferritin.

In the case of too little iron, the mRNA encoding for transferrin is bound by aconitase on the 3’-noncoding region. That way, exonucleases can not eat the mRNA and more transferrin is synthesized and more iron enters the cells.

In the case of too much iron, the aconitase binds the iron and exonucleases can eat the mRNA so iron is not absorbed in the cell.

When there is too little iron in the cell, the apoferritin mRNA is bounded by aconitase at the 5’noncoding region. The small subunit can not scan the mRNA and can not attach to it, so no apoferritin is synthesized and no iron is stored.

When there is too much iron, the aconitase binds to the iron, and the small ribosome subunit scans and binds the mRNA, more apoferritin is synthesized and more iron is stored for later use.

Translational regulation can also involve reversible phosphorilation of elongation factors. This is the best understood means og overall regulation of translation.

Under conditions that include nutrint starvation, heat shock and viral infection, eIF-2a is phosphorylated. The mechanism is the following:

1. the phosphorylated eIF-2a-GDP binds tightly to eIF-2b. (eIF-2b is necessary for nucleotide excanhge, converting eIF-2a-GDP into the functional eIF-2a-GTP)
2. since no eIF-2b is available for nucleotide exchange, the initiation factor eIF-2a-GTP is not produced, and no transaltion occurs

tilbage til molekylær biologi