title: Role of Auf1 in elimination of oxidatively damaged messenger RNA in human cells.
abstract: In aerobically growing cells, in which reactive oxygen species are produced, the guanine base of RNA is oxidized to 8-oxo-7,8-dihydroguanine, which induces alterations in gene expression. Here we show that the human Auf1 protein, also called HNRNPD, binds specifically to RNA containing this oxidized base and may be involved in cellular processes associated with managing the problems caused by RNA oxidation. Auf1-deficient cells were constructed from human HeLa and Nalm-6 lines using two different targeting procedures. Both types of Auf1-deficient cells are viable, but exhibit growth retardation. The stability of messenger RNA for four different housekeeping genes was determined in Auf1-deficient and -proficient cells, treated with or without hydrogen peroxide. The level of oxidized messenger RNA was considerably higher in Auf1-deficient cells than in Auf1-proficient cells. Auf1 may play a role in the elimination of oxidized RNA, which is required for the maintenance of proper gene expression under conditions of oxidative stress.
authors.affiliation: Frontier Research Center and Department of Biochemistry, Fukuoka Dental College, Fukuoka 814-0193, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ishii
authors.affiliation: Frontier Research Center and Department of Biochemistry, Fukuoka Dental College, Fukuoka 814-0193, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hayakawa
authors.affiliation: Department of Molecular Biology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sekiguchi
authors.affiliation: Graduate School of Nanobioscience, Yokohama City University, Yokohama 236-0027, Japan.
authors.forename: Noritaka
authors.initials: N
authors.lastname: Adachi
authors.affiliation: Frontier Research Center and Department of Biochemistry, Fukuoka Dental College, Fukuoka 814-0193, Japan. Electronic address: mseki@college.fdcnet.ac.jp.
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Sekiguchi
mesh_terms: D002460:Cell Line; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000502:physiology*; D006801:Humans; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000378:metabolism*
chemical_list: C000630986:HNRNPD protein, human; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; D012333:RNA, Messenger
keywords: 8-Oxo-7,8-dihydroguanine; Auf1 protein; Free radicals; Oxidative stress; Oxidized RNA; RNA degradation