Degradation by the 2',5'‐phosphodiesterase activity of mouse cells requires the presence of a ribo hydroxyl group in the penultimate position of the oligonucleotide substrate

Abstract

A series of 9‐β‐D‐xylofuranosyladenine (xyloA or xyloadenosine) substituted analogs of 2‐5A core trimer and tetramer were examined for their ability to be degraded by the 2',5'‐phosphodiesterase activity of cytoplasmic extracts of mouse L cells. Two distinct groups of xyloA‐substituted analogs could be readily discriminated. The first group contained xyloadenosine at the 2'‐termini and included A2'p5'A2'p5'(xyloA) and A2'p5'A2/p5'A2'p5'(xyloA). These oligomers behaved as did their parent oligoadenylates in that they were equally sensitive to degradation by the 2',5'‐phosphodiesterase activity. The second group of oligonucleotides bore a xyloadenosine residue in the penultimate nucleotide residues of the oligomers and included A2'p5'(xyloA)2'p5'(xyloA), (xyloA)2'p5'(xyloA)2'p5'(xyloA), A2'p5'A2'p5'(xyloA)2'p5'(xyloA) and (xyloA)2'p5' (xyloA)2'p5'(xyloA)2'p5'(xyloA). This group was quite resistant to 2',5'‐phosphodiesterase activity. In all, the findings demonstrate that the ribo configuration 3'‐hydroxyl group in the penultimate nucleotide of the oligonucleotide substrate is a prerequisite for the 2',5'‐phosphodiesterase activity.

Crystallization and preliminary X-ray crystallographic analysis of human phosphodiesterase 12

“…PDE12, an enzyme that belongs to the endonuclease/exonuclease/ phosphatase family, hydrolyzes 2-5A to ATP and AMP and is therefore also referred to as 2 0 ,5 0 -phosphodiesterase (2 0 ,5 0 -PDE; Itkes et al, 1984;Alster et al, 1986;Torrence et al, 1987;Johnston & Hearl, 1987;Kubota et al, 2004). It plays a role as a negative regulator in the 2-5A system by reducing 2-5A levels in cells.…”