Adenosine deaminases that act on RNA induce reproducible changes in abundance and sequence of embryonic miRNAs
- Cornelia Vesely1,
- Stefanie Tauber2,
- Fritz J Sedlazeck2,
- Arndt von Haeseler2 and
- Michael F Jantsch1,3
- 1 Department of Chromosome Biology, Max F. Perutz Laboratories, University of Vienna;
- 2 Center for Integrative Bioinformatics Vienna Max F. Perutz Laboratories, University of Vienna
- ↵* Corresponding author; email: michael.jantsch{at}univie.ac.at
Abstract
Adenosine deaminases that act on RNA bind double-stranded and structured RNAs and convert adenosines to inosines by hydrolytic deamination. Inosines are recognized as guanosines and hence, RNA editing alters the sequence information but also structure of RNAs. Editing by ADARs is widespread and essential for normal life and development. Precursors of miRNAs are abundantly edited by ADARs but neither the abundance nor the consequences of miRNA editing has been firmly established. Using transgenic mouse embryos that are deficient in the two enzymatically active editing enzymes ADAR1 and ADAR2 we compare relative frequencies but also sequence composition of miRNAs in these genetically modified backgrounds to wild-type mice by next gen sequencing. Deficiency of ADAR2 leads to a reproducible change in abundance of specific miRNAs and their predicted targets. Changes in miRNA abundance seem unrelated to editing events. Additional deletion of ADAR1 has surprisingly little impact on the mature miRNA repertoire, indicating that miRNA expression is primarily dependent on ADAR2. A to G transitions reflecting A to I editing events can be detected at few sites and at low frequency during the early embryonic stage investigated. Again, most editing events are ADAR2 dependent with only few editing sites being specifically edited by ADAR1. Besides known editing events in miRNAs a few novel, previously unknown editing events were identified. A large fraction of editing events is located to the seed region of miRNAs opening the possibility that editing leads to retargeting of these miRNAs.
- Received October 6, 2011.
- Accepted February 1, 2012.
- Copyright © 2012, Cold Spring Harbor Laboratory Press
This manuscript is Open Access.
