PDE12 cleaves 2'-5' oligoadenylates

Stable Identifier
Reaction [transition]
Homo sapiens
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Viral infection produces dsRNA that activates OAS isozymes to synthesize 5'-triphosphorylated 2'-5'-linked oligoadenylate (2-5A). Latent ribonuclease L (RNase L) binds 2-5A and oligomerizes into an active complex capable of cleaving ssRNA into retinoic acid-inducible gene-I (RIG-I) and nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing 3 (NLRP3) inflammasome-activating small RNAs (Malathi K et al. 2007; Chakrabarti A et al. 2015). Activation of RNase L can be attenuated by 2′-phosphodiesterase (PDE12)- mediated degradation of 2-5A. PDE12 is an endonuclease/exonuclease/phosphatase family member of deadenylases with both 3’,5’- and 2’,5’-phosphodiesterase activities. PDE12 localizes to the mitochondrial matrix and, in addition to degrading 2-5A, removes poly(A) tails from some mitochondrial mRNAs (Kubota K et al. 2004; Poulsen JB et al. 2011; Rorbach J et al. 2011; Silverman RH & Weiss SR 2014; Wood ER et al. 2015). The 2H phosphoesterase, AKAP7, is an unrelated nuclear enzyme that also degrades 2-5A (Gusho E et al. 2014). Several viruses, including some coronaviruses and rotaviruses, encode structurally related 2H phosphoesterases (each with two conserved histidine motifs) that degrade 2-5A and antagonize RNase L mediated antiviral activity (Zhao L et al. 2012; Zhang R et al. 2013; Silverman RH & Weiss SR 2014; Ogden KM et al. 2015; Sui B et al. 2016; Thornbrough JM et al. 2016; Goldstein SA et al. 2017).

Literature References
PubMed ID Title Journal Year
26055709 The Role of Phosphodiesterase 12 (PDE12) as a Negative Regulator of the Innate Immune Response and the Discovery of Antiviral Inhibitors

Bledsoe, R, Wood, ER, Xia, B, Deng, H, Kryn, LH, Ding, Y, Harris-Gurley, S, Chai, J, Nichols, J, Nartey, E, Sheahan, T, Wisely, B, Shotwell, JB, Nolte, RT, Tai, V, Daka, P, Rise, C, You, S, Wang, L, Smith, D, Tomberlin, G, Prabhu, N, Dickson, H, Taylor, JD

J. Biol. Chem. 2015
15231837 Identification of 2'-phosphodiesterase, which plays a role in the 2-5A system regulated by interferon

Kawaguchi, J, Furukawa, H, Matsuoka, T, Ozeki, Y, Yamashita, M, Iijima, Y, Hara, A, Yoshimura, C, Ichikawa, K, Kubota, K, Nakahara, K, Haruyama, H, Fujita, Y, Ohtsuka, T, Yoshida, S

J. Biol. Chem. 2004
Catalyst Activity

oligoribonucleotidase activity of PDE12 [cytosol]

Orthologous Events
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