RNA editing of AMPA receptor subunit GluR-B: a base-paired intron-exon structure determines position and efficiency.
A functionally critical position (Q/R site) of the AMPA receptor subunit GluR-B is controlled by RNA editing that operates in the nucleus, since in brain and clonal cell lines of neural origin, unspliced GluR-B transcripts occur edited in the Q/R site CAG codon and, additionally, in intronic adenosines. Transfection of GluR-B gene constructs into PC12 cells revealed that the proximal part of the intron downstream of the unedited exonic site is required for Q/R site editing. This intron portion contains an imperfect inverted repeat preceding a 10 nt sequence with exact complementarity to the exon centered on the unedited codon. Single nucleotide substitutions in this short intronic sequence or its exonic complement curtailed Q/R site editing, which was recovered by restoring complementarity in the respective partner strand. Base conversion in the channel-coding region of GluR-B directed by base paired sequences may be executed by a ubiquitous nuclear adenosine deaminase specific for double-stranded RNA.
Higuchi
M
M
Center for Molecular Biology, University of Heidelberg, Federal Republic of Germany.
Single
F N
FN
Köhler
M
M
Sommer
B
B
Sprengel
R
R
Seeburg
P H
PH
D000243:Adenosine Deaminase / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D015870:Gene Expression; D005796:Genes; D007438:Introns; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D016716:PC12 Cells; D017393:RNA Editing; D012323:RNA Processing, Post-Transcriptional; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics; D018091:Receptors, AMPA / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid; D015183:Restriction Mapping
D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D018091:Receptors, AMPA; D000243:Adenosine Deaminase