Disease relevance of 3AT

• The sensitivity of RNA polymerases I and II from Novikoff hepatoma (N1S1) cells to 3'-deoxyadenosine 5'-triphosphate [1].
• Conditions are described for the 3'-end labeling of RNA with 32P 3'-dATP (3'-deoxyadenosine-5'-triphosphate), a chain-terminating nucleotide, using the poly(A) polymerase (PAP) encoded by vaccinia virus [2].

High impact information on 3AT

• Since nuclear poly(A) polymerase occurs in two functional states as 'free' and 'chromatin-bound' forms, we reasoned that if the chromatin-associated poly(A) polymerase were involved in the initial polyadenylation of mRNA, it might be selectively inhibited by 3'dATP [3].
• Contrary to the in vitro observations, cordycepin 5'-triphosphate (3'dATP) is not a specific inhibitor of poly(A) synthesis in vivo, relative to RNA synthesis, and RNA polymerase I (which synthesises rRNA) is actually less sensitive to inhibition by 3'dATP than RNA polymerase II (ref. 10) (which is presumed to be involved in the synthesis of mRNA) [3].
• The structural analog of ATP, 3'-deoxyadenosine 5'-triphosphate, inhibited both the gh-L-induced and the host RNA polymerases by competing for a single binding site with ATP [4].
• Cordycepin-5'-triphosphate (3'-deoxyadenosine-5'-triphosphate) can be incorporated into the 3'-ends of DNA fragments using terminal deoxynucleotidyl transferase from calf thymus (Bollum, 1974) [5].
• Aminoacylation with valine is achieved in a rapid-equilibrium sequential random AB, ordered C mechanism indicated by bisubstrate kinetics and inhibition by 3'dATP and valinol [6].

Biological context of 3AT

• (3'-dATP), 3'-Deoxyadenosine 5'-triphosphate which is an inhibitor of the four enzymes in the aminoacylation reaction, becomes a good substrate in the PPi exchange [7].

References