title: ADAR2 affects mRNA coding sequence edits with only modest effects on gene expression or splicing in vivo.
abstract: Adenosine deaminases bind double stranded RNA and convert adenosine to inosine. Editing creates multiple isoforms of neurotransmitter receptors, such as with Gria2. Adar2 KO mice die of seizures shortly after birth, but if the Gria2 Q/R editing site is mutated to mimic the edited version then the animals are viable. We performed RNA-Seq on frontal cortices of Adar2(-/-) Gria2(R/R) mice and littermates. We found 56 editing sites with significantly diminished editing levels in Adar2 deficient animals with the majority in coding regions. Only two genes and 3 exons showed statistically significant differences in expression levels. This work illustrates that ADAR2 is important in site-specific changes of protein coding sequences but has relatively modest effects on gene expression and splicing in the adult mouse frontal cortex.
authors.affiliation: a Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health , Bethesda , MD , USA.|b Department of Neuroscience , Karolinska Institute , 171 77 Stockholm , Sweden.|c Center for Cancer Research, Laboratory of Receptor Biology and Gene Expression, National Cancer Institute , Bethesda , MD , USA.
authors.forename: Allissa A
authors.initials: AA
authors.lastname: Dillman
authors.affiliation: a Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health , Bethesda , MD , USA.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Cookson
authors.affiliation: b Department of Neuroscience , Karolinska Institute , 171 77 Stockholm , Sweden.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Galter
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D005625:Frontal Lobe / Q000378:metabolism; D015870:Gene Expression; D055786:Gene Knockout Techniques; D051379:Mice; D009154:Mutation; D017393:RNA Editing; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017423:Sequence Analysis, RNA / Q000379:methods*
chemical_list: D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C000595151:ADAR2 protein, mouse; D000243:Adenosine Deaminase
keywords: ADAR2; RNA editing; RNA-Seq