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Control of Protein Synthesis!
(i) A Mechanism for the control of protein synthesis by Adenovirus VA RNAI:
In the absence of VA RNAI protein synthesis process fails in adenovirus infected HeLa cells. This is due to defective initiation. The defect results from phosphorylation of the initiation factor elF-2 on its alpha subunit.
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The protein kinase is responsible as the DSRNA-activated inhibitor of protein synthesis (DAI) which is present in uninfected state. It is activated in cells infected with the adenovirus mutant Ad5 dl331, which producing no VA RNAI, but not in cells infected with wild-type virus.
Activation occurs during the late phase of infection with the mutant virus, and the activator appears to be DSRNA produced by symmetrical transcription of the viral genome. VA RNAI antagonizes the activation of DAI by DSRNA, but it cannot inhibit the activity of DAI once activated.
(ii) Translational Control of Protein Synthesis in Response to Heat Shock in D. Melanogaster Cells:
In response to elevated temperature, Drosophila cells synthesize a small set of proteins. This is known as the heat-shock proteins, while synthesis of most other proteins ceases. In vitro translation has been used to demonstrate that the messenger RNAs encoding the normal (25) spectrum of proteins are not broken down or irreversibly inactivated in response to the temperature change.
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During the heat shock only the heat-shock mRNAs plus a small number of preexisting mRNAs are translated, while most other messages are stored and can be reactivated upon return of the cells to their normal temperature. Cells translate both the normal mRNA and the remaining heat-shock mRNA after recovery from heat shock.
The translational control operating in intact cells has been reproduced in cell-free translation systems directed by purified mRNA from normal and heat-shocked cells. Lysates prepared from heat-shocked Drosophila cells preferentially translated the heat-shock messages, at the same time the lysate made from normally growing Drosophila cells indiscriminately translated both normal and heat-shock messages.
There must be stable alterations in the translational components of heat-shocked cells which are capable of causing selective translation of the heat-shock messages. There must be information encoded in the heat-shock messages that allows their selection.
(iii) Control of Protein Synthesis in Reticulocyte Lysates by Haemin:
When iron is lacking in the incubation medium PROTEIN synthesis in intact reticulocytes is severely restricted and can be restored by the addition of haemin l, 2. In the lysate derived from such cells, protein is synthesized at a rate similar to that in intact cells3, but finishes abruptly after a few minutes unless haemin is added 4,5.
Haemin seems to act by stabilizing the capacity of the lysate to initiate protein synthesis, because in the absence of added haemin, polysomes disappear and their associated nascent chains are released4. There is good evidence that native subunits and methionyl t-RNAF are directly involved in the process of initiation6-9.
(iv) Control of Protein Synthesis during Early Cleavage of Sheep Embryos:
Total protein synthesis is consistently high during the first 2 cleavage divisions, dropped by 95% in the 3rd cell cycle, remained low in the 4th and increased again in the 5th cycle. The studies indicate that the full activation of transcription in sheep embryos occurs in the 4th cell cycle.
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(v) The mTOR pathway in the Control of Protein Synthesis:
Amino acids, insulin, and growth factors activate signaling through mammalian target of rapamycin (mTOR) and impaired by nutrient or energy deficiency. mTOR plays key roles in cell physiology. mTOR regulates numerous components involved in protein synthesis. These initiation and elongation factor and the biogenesis of ribosomes themselves.
