RNA editing in the mammalian brain

The research of our group is focused on the process and function of RNA editing in the mammalian brain. Adenosine to inosine (A-to-I) modification is the most common type of RNA editing event found in mammals. This RNA processing event is catalyzed by a family of adenosine deaminases that act on RNA (ADARs) that convert A-to-I within double-stranded or highly structured RNA. Since inosine is recognized as guanosine by the cellular machineries, A-to-I editing has the power to recode mRNAs and also change the sequence of non-coding RNAs such as microRNAs.

Our main question is - how are substrates recognized for editing in the brain. Thousands of adenosines are targeted for editing in Alu repetitive elements in the human brain, a number of sited has also been found to recode transcripts expressed in the CNS. We are also interested in understanding how editing contributes to the variety of the transcriptome in stimulated neurons and during development.
 

Keywords

RNA editing/RNA processing/GABA-A receptor/microRNA/Alu repetitive elements

 

 

ADAR1 (red) in primary cortical neurons.

 

Selected publications

Daniel, C., Venö, M., Ekdahl, Y., Kjems, J., & Öhman, M. (2012). A distant cis acting intronic element induces site-selective RNA editing. Nucleic Acids Res. 40(19):9876-86

Ekdahl, Y., Farahani, H.S., Behm, M., Lagergren, J., & Öhman, M. (2012). A-to-I editing of microRNAs in the mammalian brain increases during development. Genome Res. 22(8):1477-87

Silberberg, G., Lundin, D., Navon, R., & Öhman, M. (2012). Deregulation of the A-to-I RNA editing mechanism in psychiatric disorders. Human Molecular Genetics. 21(2):311-321

Daniel, C., Wahlstedt, H., Ohlson, J., Björk, P., & Öhman, M. (2011). Adenosine-to-inosine RNA editing affects trafficking of the gamma-aminobutyric acid type A (GABA(A)) receptor. J Biol Chem. 286(3):2031-40

Wahlstedt, H., Daniel, C., Ensterö, M., & Öhman, M. (2009). Large-scale mRNA sequencing determines global regulation of RNA editing during brain development. Genome Research. 19:978-86