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A computational screen for site selective A-to-I editing detects novel sites in neuron specific Hu proteins
Stockholm University, Faculty of Science, Department of Molecular Biology and Functional Genomics.
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
Stockholm University, Faculty of Science, Department of Molecular Biology and Functional Genomics.
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2010 (English)In: BMC Bioinformatics, ISSN 1471-2105, Vol. 11, no 6Article in journal (Refereed) Published
Abstract [en]


Several bioinformatic approaches have previously been used to find novel sites of ADAR mediated A-to-I RNA editing in human. These studies have discovered thousands of genes that are hyper-edited in their non-coding intronic regions, especially in alu retrotransposable elements, but very few substrates that are site-selectively edited in coding regions. Known RNA edited substrates suggest, however, that site selective A-to-I editing is particularly important for normal brain development in mammals.


We have compiled a screen that enables the identification of new sites of site-selective editing, primarily in coding sequences. To avoid hyper-edited repeat regions, we applied our screen to the alu-free mouse genome. Focusing on the mouse also facilitated better experimental verification. To identify candidate sites of RNA editing, we first performed an explorative screen based on RNA structure and genomic sequence conservation. We further evaluated the results of the explorative screen by determining which transcripts were enriched for A-G mismatches between the genomic template and the expressed sequence since the editing product, inosine (I), is read as guanosine (G) by the translational machinery. For expressed sequences, we only considered coding regions to focus entirely on re-coding events. Lastly, we refined the results from the explorative screen using a novel scoring scheme based on characteristics for known A-to-I edited sites. The extent of editing in the final candidate genes was verified using total RNA from mouse brain and 454 sequencing.


Using this method, we identified and confirmed efficient editing at one site in the Gabra3 gene. Editing was also verified at several other novel sites within candidates predicted to be edited. Five of these sites are situated in genes coding for the neuron-specific RNA binding proteins HuB and HuD.

Place, publisher, year, edition, pages
BCM Journals , 2010. Vol. 11, no 6
National Category
Natural Sciences
URN: urn:nbn:se:su:diva-35079DOI: 10.1186/1471-2105-11-6ISI: 000275198500001OAI: diva2:286332
authorCount :7Available from: 2010-01-14 Created: 2010-01-14 Last updated: 2011-01-05Bibliographically approved
In thesis
1. The multi-faceted RNA molecule: Characterization and Function in the regulation of Gene Expression
Open this publication in new window or tab >>The multi-faceted RNA molecule: Characterization and Function in the regulation of Gene Expression
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In this thesis I have studied the RNA molecule and its function and characteristics in the regulation of gene expression. I have focused on two events that are important for the regulation of the transcriptome: Translational regulation through micro RNAs; and RNA editing through adenosine deaminations.

Micro RNAs (miRNAs) are ~22 nucleotides long RNA molecules that by semi complementarity bind to untranslated regions of a target messenger RNA (mRNA). The interaction manifests through an RNA/protein complex and act mainly by repressing translation of the target mRNA. I have shown that a pre-cursor miRNA molecule have significantly different information content of sequential composition of the two arms of the pre-cursor hairpin. I have also shown that sequential composition differs between species.

Selective adenosine to inosine (A-to-I) RNA editing is a post-transcriptional process whereby highly specific adenosines in a (pre-)messenger transcript are deaminated to inosines. The deamination is carried out by the ADAR family of proteins and require a specific sequential and structural landscape for target recognition. Only a handful of messenger substrates have been found to be site selectively edited in mammals. Still, most of these editing events have an impact on neurotransmission in the brain.

In order to find novel substrates for A-to-I editing, an experimental setup was made to extract RNA targets of the ADAR2 enzyme. In concert with this experimental approach, I have constructed a computational screen to predict specific positions prone to A-to-I editing.

Further, I have analyzed editing in the mouse brain at four different developmental stages by 454 amplicon sequencing. With high resolution, I present data supporting a general developmental regulation of A-to-I editing. I also present data of coupled editing events on single RNA transcripts suggesting an A-to-I editing mechanism that involve ADAR dimers to act in concert. A different editing pattern is seen for the serotonin receptor 5-ht2c.

Place, publisher, year, edition, pages
Stockholm: Institutionen för molekylärbiologi och funktionsgenomik, 2008. 52 p.
Molecular biology, Computational Biology
National Category
Biochemistry and Molecular Biology
Research subject
Molecular Biology
urn:nbn:se:su:diva-7729 (URN)978-91-7155-587-8 (ISBN)
Public defence
2008-05-30, sal E306, Arrheniuslaboratorierna, Svante Arrhenius väg 14-18, Stockholm, 13:00
Available from: 2008-05-08 Created: 2008-05-08 Last updated: 2011-01-05Bibliographically approved

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Lundin, DanielÖhman, Marie
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