3. Cordycepin inhibits poly(A) synthesis at low concentrations and RNA synthesis
ID: 213674 • Letter: 3
Question
3. Cordycepin inhibits poly(A) synthesis at low concentrations and RNA synthesis at higher concentrations. It is in clinical trials to treat leukemia (15 points). HO-Cle Cordycepin (3*-deoxyadenosine) a. What is the basis of inhibition by cordycepin? b. Why is poly(A) synthesis more sensitive than the synthesis of other RNAs to the presence of cordycepin? c. Does cordycepin need to be modified in the cell to exert its effect? 4. In a clever experiment performed in 1962, a cysteine that was already attached to tRNA °ys was chemically converted to an alanine. These alanyl-tRNA©ys molecules were then added to a cell-free translation system from which normal cysteinyl-tRNAºys molecules had been removed. When a resulting translated protein was analyzed, it was found that alanine had been inserted at every point in the protein chain where cysteine was supposed to be. Discuss what this experiment tells you about the role of aminoacyl- tRNA synthetases during the normal translation of the genetic code (10 points).Explanation / Answer
a) Cordycepin is a nucleoside antimetabolite which is isolated from Cordyceps militaris with potential antineoplastic activity. Cordycepin is an adenosine analog. Triphosphate cordycepin can be incorporated into RNA which then inhibits transcription elongation and RNA synthesis due to the absence of a hydroxyl moiety at the 3' position.
b)Cordycepin has been reported to shorten the poly A tail of mRNA which further affects its stability inside the cytoplasm. It was observed that inhibition of polyadenylation with Cordycepin of some m-RNAs made them more sensitive than the other mRNAs.
c) Cordycepin is readily phosphorylated to its mono-, di-, and triphosphate intracellularly. Triphosphate cordycepin then acts on RNA synthesis.
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