Poster abstracts
Poster number 151 submitted by Boyoon Yang
Gathering insights into differences between substrate recognition by ADR-1 and ADR-2 in vivo
Boyoon Yang (Biochemistry Graduate Program, Indiana University Bloomington, IN ), Ryan J. Andrews, Brenda L. Bass (2Department of Biochemistry, University of Utah, UT), Douglas B. Rusch (Center for Genomics and Bioinformatics, Indiana University, Bloomington, IN), Heather A. Hundley (Department of Biology, Indiana University Bloomington, IN )
Abstract:
All animals generate transcriptomic diversity by modifying genetic information through RNA editing. A-to-I RNA editing is mediated by Adenosine deaminases that act on RNA (ADARs). ADARs convert specific adenosines into inosines in double-stranded RNA (dsRNA). ADARs have a high potential as therapeutic means to correct specific G-to-A mutations at the RNA level without modifying the genome. Therefore, it is crucial to understand how ADARs bind specific transcripts and select an individual adenosine for editing in vivo.
In Caenorhabditis elegans, RNA editing is mediated by ADR-2, whereas ADR-1 is an editing-deficient ADAR family member which positively or negatively regulates editing by ADR-2. While in vitro studies have shown that ADARs bind dsRNA in a structure-dependent manner, how ADARs recognize specific dsRNA substrates in vivo is poorly understood. To investigate how ADR-1 and ADR-2 bind specific targets, we performed chimeric crosslinking immunoprecipitation (CLIP) coupled to high-throughput sequencing. ADR-1/ADR-2 eCLIP revealed that the majority of ADR-1 binding occurs at 3’ UTRs, while most ADR-2 binding occurs at intronic regions, indicating ADR-1 and ADR-2 may recognize substrates differently. Elucidating the mechanism of how ADR-1 and ADR-2 co-occupy target mRNAs will provide new insights into how A-to-I editing is mediated in vivo.
Keywords: RNA editing, ADAR, Substrate specificity