Human polynucleotide phosphorylase protein in response to oxidative stress.
8-Oxo-7,8-dihydroguanine (8-oxoGua) is generated in nucleic acids as well as in their precursors due to the actions of oxygen radicals produced through a normal cellular metabolism. Since oxidized guanine can pair with both cytosine and adenine, it causes alterations in the phenotypic expression when it is present in RNA. To prevent such an outcome, organisms must have some mechanism for eliminating such oxidized guanine nucleotides from RNA and its precursors. In mammalian cells, MTH1 and NUDT5 proteins degrade 8-oxoGTP and 8-oxoGDP to 8-oxoGMP, which is an unusable form for RNA synthesis. In a search for proteins functioning at the RNA level, polynucleotide phosphorylase (PNP) protein has been suggested to be a good candidate for such a role. The human PNP protein has an ability to bind specifically to RNA containing 8-oxoGua. When human cells are exposed to agents that induce oxidative stress, such as hydrogen peroxide and menadion, the amounts of PNP protein decrease rapidly while amounts of other proteins in the cells do not change after such treatments. No specific decrease in the PNP protein level is observed when cells are treated with ACNU and cycloheximide at doses sufficient to provide the same degree of growth suppression. These results imply that the PNP protein might thus play a role in excluding oxidized forms of RNA from the translation mechanism.
Hayakawa
Hiroshi
H
Department of Medical Biochemistry, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. hiroshi@med.kyushu-u.ac.jp
Sekiguchi
Mutsuo
M
D001483:Base Sequence; D017931:DNA Primers; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D018384:Oxidative Stress; D011117:Polyribonucleotide Nucleotidyltransferase / Q000378:metabolism*; D011485:Protein Binding; D012313:RNA / Q000096:biosynthesis; D034741:RNA, Small Interfering
D017931:DNA Primers; D034741:RNA, Small Interfering; D012313:RNA; D011117:Polyribonucleotide Nucleotidyltransferase