Article ; Online: Steric antisense inhibition of AMPA receptor Q/R editing reveals tight coupling to intronic editing sites and splicing.
2012 Volume 41, Issue 2, Page(s) 1113–1123
Abstract: ... the most efficiently edited site--the AMPA receptor GluA2 Q/R site. We show that inhibition of editing ...
| Abstract | Adenosine-to-Inosine (A-to-I) RNA editing is a post-transcriptional mechanism, evolved to diversify the transcriptome in metazoa. In addition to wide-spread editing in non-coding regions protein recoding by RNA editing allows for fine tuning of protein function. Functional consequences are only known for some editing sites and the combinatorial effect between multiple sites (functional epistasis) is currently unclear. Similarly, the interplay between RNA editing and splicing, which impacts on post-transcriptional gene regulation, has not been resolved. Here, we describe a versatile antisense approach, which will aid resolving these open questions. We have developed and characterized morpholino oligos targeting the most efficiently edited site--the AMPA receptor GluA2 Q/R site. We show that inhibition of editing closely correlates with intronic editing efficiency, which is linked to splicing efficiency. In addition to providing a versatile tool our data underscore the unique efficiency of a physiologically pivotal editing site. |
|---|---|
| MeSH term(s) | Adenosine/metabolism ; Amino Acid Sequence ; Animals ; Cell Line ; Humans ; Inosine/metabolism ; Introns ; Molecular Sequence Data ; Morpholinos ; Oligonucleotides, Antisense ; RNA Editing ; RNA Splicing ; Receptors, AMPA/genetics |
| Chemical Substances | Morpholinos ; Oligonucleotides, Antisense ; Receptors, AMPA ; Inosine (5A614L51CT) ; Adenosine (K72T3FS567) ; glutamate receptor ionotropic, AMPA 2 (P6W5IXV8V9) |
| Language | English |
| Publishing date | 2012-11-20 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 186809-3 |
| ISSN | 1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048 |
| ISSN (online) | 1362-4962 ; 1362-4954 |
| ISSN | 0301-5610 ; 0305-1048 |
| DOI | 10.1093/nar/gks1044 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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