title: Stress-induced apoptosis associated with null mutation of ADAR1 RNA editing deaminase gene.
abstract: One type of RNA editing involves the conversion of adenosine residues into inosine in double-stranded RNA through the action of adenosine deaminases acting on RNA (ADAR). A-to-I RNA editing of the coding sequence could result in synthesis of proteins not directly encoded in the genome. ADAR edits also non-coding sequences of target RNAs, such as introns and 3'-untranslated regions, which may affect splicing, translation, and mRNA stability. Three mammalian ADAR gene family members (ADAR1-3) have been identified. Here we investigated phenotypes of mice homozygous for ADAR1 null mutation. Although live ADAR1-/- embryos with normal gross appearance could be recovered up to E11.5, widespread apoptosis was detected in many tissues. Fibroblasts derived from ADAR1-/- embryos were also prone to apoptosis induced by serum deprivation. Our results demonstrate an essential requirement for ADAR1 in embryogenesis and suggest that it functions to promote survival of numerous tissues by editing one or more double-stranded RNAs required for protection against stress-induced apoptosis.
authors: The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
authors: Qingde
authors: Q
authors: Wang
authors: Mana
authors: M
authors: Miyakoda
authors: Weidong
authors: W
authors: Yang
authors: Jaspal
authors: J
authors: Khillan
authors: David L
authors: DL
authors: Stachura
authors: Mitchell J
authors: MJ
authors: Weiss
authors: Kazuko
authors: K
authors: Nishikura
mesh_terms: D000243:Adenosine Deaminase / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics* / Q000502:physiology*; D001483:Base Sequence; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000235:genetics; D005314:Embryonic and Fetal Development / Q000235:genetics / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology; D008099:Liver / Q000196:embryology / Q000201:enzymology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D016513:Mice, SCID; D010641:Phenotype; D011247:Pregnancy; D017393:RNA Editing / Q000235:genetics* / Q000502:physiology*; D016601:RNA-Binding Proteins; D013312:Stress, Physiological / Q000201:enzymology / Q000235:genetics / Q000473:pathology
chemical_list: D018076:DNA, Complementary; D016601:RNA-Binding Proteins; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase