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Editing inducer elements increases A-to-I editing efficiency in the mammalian transcriptome
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
Number of Authors: 4
2017 (English)In: Genome Biology, ISSN 1465-6906, E-ISSN 1474-760X, Vol. 18, 195Article in journal (Refereed) Published
Abstract [en]

Background: Adenosine to inosine (A-to-I) RNA editing has been shown to be an essential event that plays a significant role in neuronal function, as well as innate immunity, in mammals. It requires a structure that is largely double-stranded for catalysis but little is known about what determines editing efficiency and specificity in vivo. We have previously shown that some editing sites require adjacent long stem loop structures acting as editing inducer elements (EIEs) for efficient editing. Results: The glutamate receptor subunit A2 is edited at the Q/R site in almost 100% of all transcripts. We show that efficient editing at the Q/R site requires an EIE in the downstream intron, separated by an internal loop. Also, other efficiently edited sites are flanked by conserved, highly structured EIEs and we propose that this is a general requisite for efficient editing, while sites with low levels of editing lack EIEs. This phenomenon is not limited to mRNA, as non-coding primary miRNAs also use EIEs to recruit ADAR to specific sites. Conclusions: We propose a model where two regions of dsRNA are required for efficient editing: first, an RNA stem that recruits ADAR and increases the local concentration of the enzyme, then a shorter, less stable duplex that is ideal for efficient and specific catalysis. This discovery changes the way we define and determine a substrate for A-to-I editing. This will be important in the discovery of novel editing sites, as well as explaining cases of altered editing in relation to disease.

Place, publisher, year, edition, pages
2017. Vol. 18, 195
Keyword [en]
RNA editing, Adenosine deamination, Glutamate receptor, ADAR, EIE, miRNA
National Category
Environmental Biotechnology Biological Sciences
Identifiers
URN: urn:nbn:se:su:diva-148990DOI: 10.1186/s13059-017-1324-xISI: 000413577600002PubMedID: 29061182OAI: oai:DiVA.org:su-148990DiVA: diva2:1160820
Available from: 2017-11-28 Created: 2017-11-28 Last updated: 2017-11-28Bibliographically approved

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Daniel, ChammiranWidmark, AlbinÖhman, Marie
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