RNA editing in the mammalian brain
In recent years proofs of the eukaryotic messenger RNA as a target for gene regulation and sequence alteration has vastly expanded. New technologies such as high throughput sequencing of entire transcriptomes have revealed that alternative RNA processing events are used to increase the diversity of the proteome to a much larger extent than previously anticipated. By alternative splicing, alternative polyadenylation and RNA editing the possibilities to diversify and regulate the RNA population are almost infinite. In addition an increasing number of non-coding RNAs such as microRNAs, have been discovered to contribute to tissue specific and developmentally regulated transcriptome variation.
Our research is focused on functional consequences of adenosine to inosine (A-to-I) RNA editing, the most common type of editing in mammals. This RNA processing event is catalyzed by the ADAR enzymes, converting 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. Most recoding sites of editing have been found in transcripts important for neurotransmission, and a number of brain specific microRNA are also edited. We are therefore particularly interested in the function of RNA editing in neurons and in understanding how editing contributes to the variety of the transcriptome during brain development and neuronal stimulation.
RNA editing/RNA processing/ADAR/microRNA/neuron.
Daniel, C. Silberberg, G. Behm, M. Öhman, M. (2014) Alu elements shape the primate transcriptome by cis-regulation of RNA editing. Genome Biol. 15(2):R28.
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
(Link to Researcher ID)
January 26, 2016
Page editor: Elin Eriksson
Source: Department of Molecular Biosciences, The Wenner-Gren Institute