Talk abstracts

Talk on Saturday 09:45-10:00am submitted by Aparna Anantharaman

ADARs Antagonize Deadenylase-dependent Destabilization of a Nuclear-retained RNA

Aparna Anantharaman (Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign), Vidisha Tripathi (National Center for Cell Science, Pune, India), Kannanganattu V. Prasanth, Abid Khan, Supriya G. Prasanth (Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign), Je-Hyun Yoon, Myriam Gorospe (Laboratory of Genetics, National Institute of Aging-Intramural Research program, NIH), Johan Ohlson, Helene Wahlstedt, Marie Ohman, Shuomeng Guang, Jian Ma (Department of Molecular Biosciences, the WennerGren Institute, Stockholm University, Sweden, Department of Bioengineering, Carl R. Woese Institute for Genomic Biology, UIUC), Jochen C. Hartner, Shinichi Nakagawa, Tetsuro Hirose, Michael F. Jantsch (TaconicArtemis GmbH, Germany, RNA Biology Laboratory, RIKEN, JAPAN, Institute of Genetic Medicine, Hokkaido University, Japan, Department of Chromosome Biology, Max F. Perutz Laboratories, Austria)

Adenosine deaminases acting on RNA (ADAR) catalyze the editing of adenosine to inosine (A-to-I) within RNA sequences. Most A-to-I editing occurs in noncoding repeat sequences, including introns and UTRs (un-translated regions). The functional significance of this deamination is poorly understood. Here, we demonstrate that ADAR association with the 3’UTR of nuclear-retained Ctn RNA (Cat2 transcribed nuclear RNA) promotes the stability of Ctn RNA. In the absence of ADAR, the cellular abundance and half-life of Ctn RNA are significantly reduced. Unedited Ctn RNA has a shortened poly(A) tail and shows enhanced interaction with PARN [poly(A)-specific ribonuclease] deadenylase. Furthermore, the RNA binding protein HuR/ELAVL1 recruits PARN to unedited Ctn RNA. Our results show that ADAR promotes the stability of Ctn RNA by antagonizing its degradation by PARN and HuR. In addition to Ctn RNA, global transcriptomic analysis revealed that other mRNAs including nuclear and long noncoding RNAs are also stabilized by ADAR. Taken together, our findings suggest a regulatory paradigm wherein ADARs enhance target mRNA stability, by limiting the interaction of RNA-destabilizing proteins with their cognate substrates.

Keywords: ADAR, Ctn RNA, mRNA stability