Describe how cells control the size of the poly-A tail on mRNA molecules in order to regulate translation initiation. Next explain how a kinase inhibitor could decrease gene expression in regards to polyadenylation? Your answer should include the

Question

following proteins in your answer: Maskin, PARN, CPEB, eIF4E, eIF4G, and Poly-A polymerase.

What will be an ideal response?

Answer 1

Typically, an mRNA cannot initiate translation unless it has a sufficiently long poly-A tail at the 3' end of the mRNA. To inhibit translation initiation, a protein called CPEB binds to the CPE sequence on the mRNA. This will then bring in an enzyme called PARN. PARN is a ribonuclease that shortens the poly-A tail. In addition, CPEB also recruits the protein called Maskin. Maskin binds to the translation initiation factor called eIF4E. This prevents eIF4E from binding to eIF4G, which now blocks initiation. Together this keeps the 3' poly-A tail short and blocks the interaction of the two IF proteins. To initiate translation, the protein CPEB gets phosphorylated by a specific kinase. This causes a conformational change that excludes both Maskin and PARN. With these two proteins gone, now the poly-A tail can extend and eIF4E and eIF4G can interact with each other to initiate translation.
If a kinase inhibitor was introduced, then CPEB would not be phosphorylated, so no conformational change would occur, and the Maskin and PARN would be able to continue to exert their inhibitory effect on translation initiation.