Editing inducer elements increases A-to-I editing efficiency in the mammalian transcriptome
Abstract 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 deter...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2017-10-01
|
| Series: | Genome Biology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13059-017-1324-x |
| _version_ | 1818025022107680768 |
|---|---|
| author | Chammiran Daniel Albin Widmark Ditte Rigardt Marie Öhman |
| author_facet | Chammiran Daniel Albin Widmark Ditte Rigardt Marie Öhman |
| author_sort | Chammiran Daniel |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-10T04:09:30Z |
| format | Article |
| id | doaj.art-6c9252a86b884ea3b48df8b8286920a9 |
| institution | Directory Open Access Journal |
| issn | 1474-760X |
| language | English |
| last_indexed | 2024-12-10T04:09:30Z |
| publishDate | 2017-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Genome Biology |
| spelling | doaj.art-6c9252a86b884ea3b48df8b8286920a92022-12-22T02:02:46ZengBMCGenome Biology1474-760X2017-10-0118111610.1186/s13059-017-1324-xEditing inducer elements increases A-to-I editing efficiency in the mammalian transcriptomeChammiran Daniel0Albin Widmark1Ditte Rigardt2Marie Öhman3Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm UniversityDepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm UniversityDepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm UniversityDepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm UniversityAbstract 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.http://link.springer.com/article/10.1186/s13059-017-1324-xRNA editingAdenosine deaminationGlutamate receptorADAREIEmiRNA |
| spellingShingle | Chammiran Daniel Albin Widmark Ditte Rigardt Marie Öhman Editing inducer elements increases A-to-I editing efficiency in the mammalian transcriptome Genome Biology RNA editing Adenosine deamination Glutamate receptor ADAR EIE miRNA |
| title | Editing inducer elements increases A-to-I editing efficiency in the mammalian transcriptome |
| title_full | Editing inducer elements increases A-to-I editing efficiency in the mammalian transcriptome |
| title_fullStr | Editing inducer elements increases A-to-I editing efficiency in the mammalian transcriptome |
| title_full_unstemmed | Editing inducer elements increases A-to-I editing efficiency in the mammalian transcriptome |
| title_short | Editing inducer elements increases A-to-I editing efficiency in the mammalian transcriptome |
| title_sort | editing inducer elements increases a to i editing efficiency in the mammalian transcriptome |
| topic | RNA editing Adenosine deamination Glutamate receptor ADAR EIE miRNA |
| url | http://link.springer.com/article/10.1186/s13059-017-1324-x |
| work_keys_str_mv | AT chammirandaniel editinginducerelementsincreasesatoieditingefficiencyinthemammaliantranscriptome AT albinwidmark editinginducerelementsincreasesatoieditingefficiencyinthemammaliantranscriptome AT ditterigardt editinginducerelementsincreasesatoieditingefficiencyinthemammaliantranscriptome AT marieohman editinginducerelementsincreasesatoieditingefficiencyinthemammaliantranscriptome |