title: ADAR2 regulates RNA stability by modifying access of decay-promoting RNA-binding proteins.
abstract: Adenosine deaminases acting on RNA (ADARs) catalyze the editing of adenosine residues to inosine (A-to-I) within RNA sequences, mostly in the introns and UTRs (un-translated regions). The significance of editing within non-coding regions of RNA is poorly understood. Here, we demonstrate that association of ADAR2 with RNA stabilizes a subset of transcripts. ADAR2 interacts with and edits the 3΄UTR of nuclear-retained Cat2 transcribed nuclear RNA (Ctn RNA). In absence of ADAR2, the abundance and half-life of Ctn RNA are significantly reduced. Furthermore, ADAR2-mediated stabilization of Ctn RNA occurred in an editing-independent manner. Unedited Ctn RNA shows enhanced interaction with the RNA-binding proteins HuR and PARN [Poly(A) specific ribonuclease deadenylase]. HuR and PARN destabilize Ctn RNA in absence of ADAR2, indicating that ADAR2 stabilizes Ctn RNA by antagonizing its degradation by PARN and HuR. Transcriptomic analysis identified other RNAs that are regulated by a similar mechanism. In summary, we identify a regulatory mechanism whereby ADAR2 enhances target RNA stability by limiting the interaction of RNA-destabilizing proteins with their cognate substrates.
authors.affiliation: Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, 601 S Goodwin Avenue, Urbana, IL 61801, USA.
authors.forename: Aparna
authors.initials: A
authors.lastname: Anantharaman
authors.affiliation: Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, 601 S Goodwin Avenue, Urbana, IL 61801, USA.
authors.forename: Vidisha
authors.initials: V
authors.lastname: Tripathi
authors.affiliation: Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, 601 S Goodwin Avenue, Urbana, IL 61801, USA.
authors.forename: Abid
authors.initials: A
authors.lastname: Khan
authors.affiliation: Laboratory of Genetics, National Institute of Aging-Intramural Research program, NIH, Baltimore, MD 21224, USA.
authors.forename: Je-Hyun
authors.initials: JH
authors.lastname: Yoon
authors.affiliation: Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, 601 S Goodwin Avenue, Urbana, IL 61801, USA.
authors.forename: Deepak K
authors.initials: DK
authors.lastname: Singh
authors.affiliation: Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, 601 S Goodwin Avenue, Urbana, IL 61801, USA.
authors.forename: Omid
authors.initials: O
authors.lastname: Gholamalamdari
authors.affiliation: Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Shuomeng
authors.initials: S
authors.lastname: Guang
authors.affiliation: Department of Molecular Biosciences, the WennerGren Institute, Stockholm University, SE-10691, Svante Arrheniusväg 20C, Stockholm, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Ohlson
authors.affiliation: Department of Molecular Biosciences, the WennerGren Institute, Stockholm University, SE-10691, Svante Arrheniusväg 20C, Stockholm, Sweden.
authors.forename: Helene
authors.initials: H
authors.lastname: Wahlstedt
authors.affiliation: Department of Molecular Biosciences, the WennerGren Institute, Stockholm University, SE-10691, Svante Arrheniusväg 20C, Stockholm, Sweden.
authors.forename: Marie
authors.initials: M
authors.lastname: Öhman
authors.affiliation: Center for Anatomy and Cell Biology and Department for Medical Biochemistry, Medical University of Vienna, A-1090, Vienna, Austria.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Jantsch
authors.affiliation: Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Nicholas K
authors.initials: NK
authors.lastname: Conrad
authors.affiliation: Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Ma
authors.affiliation: Laboratory of Genetics, National Institute of Aging-Intramural Research program, NIH, Baltimore, MD 21224, USA.
authors.forename: Myriam
authors.initials: M
authors.lastname: Gorospe
authors.affiliation: Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, 601 S Goodwin Avenue, Urbana, IL 61801, USA.
authors.forename: Supriya G
authors.initials: SG
authors.lastname: Prasanth
authors.affiliation: Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, 601 S Goodwin Avenue, Urbana, IL 61801, USA.
authors.forename: Kannanganattu V
authors.initials: KV
authors.lastname: Prasanth
mesh_terms: D020413:3' Untranslated Regions; D000243:Adenosine Deaminase / Q000378:metabolism*; D000818:Animals; D027202:Cationic Amino Acid Transporter 2 / Q000235:genetics / Q000378:metabolism; D000067780:ELAV-Like Protein 1 / Q000378:metabolism*; D005095:Exoribonucleases / Q000378:metabolism*; D051379:Mice; D017393:RNA Editing; D020871:RNA Stability; D062085:RNA, Long Noncoding / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D000243:Adenosine Deaminase; D027202:Cationic Amino Acid Transporter 2; D000067780:ELAV-Like Protein 1; D005095:Exoribonucleases; D062085:RNA, Long Noncoding; D016601:RNA-Binding Proteins; C000593997:Elavl1 protein, mouse; C000595151:ADAR2 protein, mouse