An inosine triphosphate pyrophosphatase safeguards plant nucleic acids from aberrant purine nucleotides

SUMMARY-In plants, inosine is enzymatically introduced in some tRNAs but not in other RNAs or DNA. Nonetheless, our data show that RNA and DNA fromArabidopsis thalianacontain (deoxy)inosine, probably derived from non-enzymatic adenosine deamination in nucleic acids and usage of (deoxy)inosine triphosphate (dITP and ITP) during nucleic acid synthesis.-We combined biochemical approaches, sample preparation and LC-MS, as well as RNA-Seq to characterize a plant INOSINE TRIPHOSPHATE PYROPHOSPHATASE (ITPA) fromArabidopsis thaliana, which is conserved in many organisms, and investigated the sources of deaminated purine nucleotides in plants.-ITPA dephosphorylates deaminated nucleoside di- and triphosphates to the respective monophosphates.ITPAloss-of-function causes inosine di- and triphosphate accumulationin vivoand an elevated (deoxy)inosine content in DNA and RNA, as well as salicylic acid (SA) accumulation, early senescence and upregulation of transcripts associated with immunity and senescence. Cadmium-induced oxidative stress leads to more ITP in the wildtype, and this effect is enhanced initpamutants, suggesting that ITP originates from ATP deamination.-ITPA is part of a molecular protection system, preventing accumulation of (d)ITP, its usage for nucleic acid synthesis, and probably nucleic acid stress leading to SA accumulation, stress gene induction and early senescence.