TY  - JOUR
A1  - Wahlstedt, Helene
A1  - Daniel, Chammiran
A1  - Ensterö, Mats
A1  - Öhman, Marie
T1  - Large-scale mRNA sequencing determines global regulation of RNA editing during brain development
Y1  - 2009/06/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 978 
EP  - 986 
DO  - 10.1101/gr.089409.108 
VL  - 19 
IS  - 6 
UR  - http://genome.cshlp.org/content/19/6/978.abstract 
N2  - RNA editing by adenosine deamination has been shown to generate multiple isoforms of several neural receptors, often with profound effects on receptor function. However, little is known about the regulation of editing activity during development. We have developed a large-scale RNA sequencing protocol to determine adenosine-to-inosine (A-to-I) editing frequencies in the coding region of genes in the mammalian brain. Using the 454 Life Sciences (Roche) Amplicon Sequencing technology, we were able to determine even low levels of editing with high accuracy. The efficiency of editing for 28 different sites was analyzed during the development of the mouse brain from embryogenesis to adulthood. We show that, with few exceptions, the editing efficiency is low during embryogenesis, increasing gradually at different rates up to the adult mouse. The variation in editing gave receptors like HTR2C and GABAA (gamma-aminobutyric acid type A) a different set of protein isoforms during development from those in the adult animal. Furthermore, we show that this regulation of editing activity cannot be explained by an altered expression of the ADAR proteins but, rather, by the presence of a regulatory network that controls the editing activity during development. 
ER  -