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- Daniel, ChammiranStockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut (author)
Editing inducer elements increases A-to-I editing efficiency in the mammalian transcriptome
- Article/chapterEnglish2017
Publisher, publication year, extent ...
- 2017-10-23
- Springer Science and Business Media LLC,2017
- printrdacarrier
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- LIBRIS-ID:oai:DiVA.org:su-148990
- https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-148990URI
- https://doi.org/10.1186/s13059-017-1324-xDOI
Supplementary language notes
- Language:English
- Summary in:English
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- 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.
Subject headings and genre
- TEKNIK OCH TEKNOLOGIER Miljöbioteknik hsv//swe
- ENGINEERING AND TECHNOLOGY Environmental Biotechnology hsv//eng
- NATURVETENSKAP Biologi hsv//swe
- NATURAL SCIENCES Biological Sciences hsv//eng
- RNA editing
- Adenosine deamination
- Glutamate receptor
- ADAR
- EIE
- miRNA
Added entries (persons, corporate bodies, meetings, titles ...)
- Widmark, AlbinStockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut(Swepub:su)alwi2546 (author)
- Rigardt, DitteStockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut (author)
- Öhman, MarieStockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut(Swepub:su)marohm (author)
- Stockholms universitetInstitutionen för molekylär biovetenskap, Wenner-Grens institut (creator_code:org_t)
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- In:Genome Biology: Springer Science and Business Media LLC181465-69061474-760X
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