Stress-induced apoptosis associated with null mutation of ADAR1 RNA editing deaminase gene.
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.
Wang
Qingde
Q
The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
Miyakoda
Mana
M
Yang
Weidong
W
Khillan
Jaspal
J
Stachura
David L
DL
Weiss
Mitchell J
MJ
Nishikura
Kazuko
K
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
D018076:DNA, Complementary; D016601:RNA-Binding Proteins; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase