title: Human proteins that specifically bind to 8-oxoguanine-containing RNA and their responses to oxidative stress.
abstract: Exposure of cells to oxygen radicals damage various biologically important molecules. Among the oxidized bases produced in nucleic acids, 8-oxo-7,8-dihydroguanine (8-oxoguanine) is particularly important since it causes base mispairing. To ensure accurate gene expression, organisms must have a mechanism to discriminate 8-oxoguanine-containing RNA from normal transcripts. We searched for proteins that specifically bind to 8-oxoguanine-containing RNA from human HeLa cell extracts, and the candidate proteins were identified using mass spectrometry. Among the identified candidates, splicing isoform 1 of heterogeneous nuclear ribonucleoprotein D0 (HNRNPD) and splicing isoform C1 of heterogeneous nuclear ribonucleoprotein C1/C2 (HNRNPC) exhibited strong abilities to bind to oxidized RNA. The amount of HNRNPD protein rapidly decreased when cells were exposed to hydrogen peroxide, an agent that enhances oxidative stress. Moreover, the suppression of HNRNPD expression by siRNA caused cells to exhibit an increased sensitivity to hydrogen peroxide. The application of siRNA against HNRNPC also caused an increase in sensitivity to hydrogen peroxide. Since no additive effect was observed with a combined addition of siRNAs for HNRNPD and HNRNPC, we concluded that the two proteins may function in the same mechanism for the accurate gene expression.
authors.affiliation: Department of Functional Bioscience and Advanced Science Research Center, Fukuoka Dental College, Fukuoka 814-0193, Japan. hiroshi@college.fdcnet.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hayakawa
authors.forename: Aya
authors.initials: A
authors.lastname: Fujikane
authors.forename: Riyoko
authors.initials: R
authors.lastname: Ito
authors.forename: Masaki
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Keiichi I
authors.initials: KI
authors.lastname: Nakayama
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Sekiguchi
mesh_terms: D006147:Guanine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D006367:HeLa Cells; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000235:genetics / Q000378:metabolism*; D034482:Heterogeneous-Nuclear Ribonucleoprotein Group C / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018384:Oxidative Stress; D012313:RNA / Q000737:chemistry / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: C000630986:HNRNPD protein, human; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; D034482:Heterogeneous-Nuclear Ribonucleoprotein Group C; D034741:RNA, Small Interfering; C024829:8-hydroxyguanine; D006147:Guanine; D012313:RNA