ADAR2 regulates RNA stability by modifying access of decay-promoting RNA-binding proteins

Aparna Anantharaman, Vidisha Tripathi, Abid Khan, Je Hyun Yoon, Deepak K. Singh, Omid Gholamalamdari, Shuomeng Guang, Johan Ohlson, Helene Wahlstedt, Marie Öhman, Michael F. Jantsch, Nicholas K. Conrad, Jian Ma, Myriam Gorospe, Supriya G. Prasanth, Kannanganattu V. Prasanth

Research output: Contribution to journalArticle

16 Citations (Scopus)

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 3Î.,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.

Original languageEnglish (US)
Pages (from-to)4189-4201
Number of pages13
JournalNucleic Acids Research
Volume45
Issue number7
DOIs
StatePublished - Apr 20 2017

Fingerprint

Nuclear RNA
RNA-Binding Proteins
RNA Stability
RNA
RNA Editing
Inosine
Untranslated RNA
Adenosine Deaminase
Adenosine
Introns
Half-Life
Proteins

ASJC Scopus subject areas

  • Genetics

Cite this

Anantharaman, A., Tripathi, V., Khan, A., Yoon, J. H., Singh, D. K., Gholamalamdari, O., ... Prasanth, K. V. (2017). ADAR2 regulates RNA stability by modifying access of decay-promoting RNA-binding proteins. Nucleic Acids Research, 45(7), 4189-4201. https://doi.org/10.1093/nar/gkw1304

ADAR2 regulates RNA stability by modifying access of decay-promoting RNA-binding proteins. / Anantharaman, Aparna; Tripathi, Vidisha; Khan, Abid; Yoon, Je Hyun; Singh, Deepak K.; Gholamalamdari, Omid; Guang, Shuomeng; Ohlson, Johan; Wahlstedt, Helene; Öhman, Marie; Jantsch, Michael F.; Conrad, Nicholas K.; Ma, Jian; Gorospe, Myriam; Prasanth, Supriya G.; Prasanth, Kannanganattu V.

In: Nucleic Acids Research, Vol. 45, No. 7, 20.04.2017, p. 4189-4201.

Research output: Contribution to journalArticle

Anantharaman, A, Tripathi, V, Khan, A, Yoon, JH, Singh, DK, Gholamalamdari, O, Guang, S, Ohlson, J, Wahlstedt, H, Öhman, M, Jantsch, MF, Conrad, NK, Ma, J, Gorospe, M, Prasanth, SG & Prasanth, KV 2017, 'ADAR2 regulates RNA stability by modifying access of decay-promoting RNA-binding proteins', Nucleic Acids Research, vol. 45, no. 7, pp. 4189-4201. https://doi.org/10.1093/nar/gkw1304
Anantharaman A, Tripathi V, Khan A, Yoon JH, Singh DK, Gholamalamdari O et al. ADAR2 regulates RNA stability by modifying access of decay-promoting RNA-binding proteins. Nucleic Acids Research. 2017 Apr 20;45(7):4189-4201. https://doi.org/10.1093/nar/gkw1304
Anantharaman, Aparna ; Tripathi, Vidisha ; Khan, Abid ; Yoon, Je Hyun ; Singh, Deepak K. ; Gholamalamdari, Omid ; Guang, Shuomeng ; Ohlson, Johan ; Wahlstedt, Helene ; Öhman, Marie ; Jantsch, Michael F. ; Conrad, Nicholas K. ; Ma, Jian ; Gorospe, Myriam ; Prasanth, Supriya G. ; Prasanth, Kannanganattu V. / ADAR2 regulates RNA stability by modifying access of decay-promoting RNA-binding proteins. In: Nucleic Acids Research. 2017 ; Vol. 45, No. 7. pp. 4189-4201.
@article{c45ea087aaf341038ee845c94e08f272,
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{\^I}.,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.",
author = "Aparna Anantharaman and Vidisha Tripathi and Abid Khan and Yoon, {Je Hyun} and Singh, {Deepak K.} and Omid Gholamalamdari and Shuomeng Guang and Johan Ohlson and Helene Wahlstedt and Marie {\"O}hman and Jantsch, {Michael F.} and Conrad, {Nicholas K.} and Jian Ma and Myriam Gorospe and Prasanth, {Supriya G.} and Prasanth, {Kannanganattu V.}",
year = "2017",
month = "4",
day = "20",
doi = "10.1093/nar/gkw1304",
language = "English (US)",
volume = "45",
pages = "4189--4201",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "7",

}

TY - JOUR

T1 - ADAR2 regulates RNA stability by modifying access of decay-promoting RNA-binding proteins

AU - Anantharaman, Aparna

AU - Tripathi, Vidisha

AU - Khan, Abid

AU - Yoon, Je Hyun

AU - Singh, Deepak K.

AU - Gholamalamdari, Omid

AU - Guang, Shuomeng

AU - Ohlson, Johan

AU - Wahlstedt, Helene

AU - Öhman, Marie

AU - Jantsch, Michael F.

AU - Conrad, Nicholas K.

AU - Ma, Jian

AU - Gorospe, Myriam

AU - Prasanth, Supriya G.

AU - Prasanth, Kannanganattu V.

PY - 2017/4/20

Y1 - 2017/4/20

N2 - 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 3Î.,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.

AB - 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 3Î.,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.

UR - http://www.scopus.com/inward/record.url?scp=85019119242&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85019119242&partnerID=8YFLogxK

U2 - 10.1093/nar/gkw1304

DO - 10.1093/nar/gkw1304

M3 - Article

VL - 45

SP - 4189

EP - 4201

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 7

ER -