Q/R site editing in kainate receptor GluR5 and GluRG pre-mRNAs requires distant intronic sequences
Q/R site editing in kainate receptor GluR5 and GluRG pre-mRNAs requires distant intronic sequences
复制标题
DOI：
10.1073/pnas.93.5.1875
复制
发表时间：
1996-03-05
影响因子：
11.1
通讯作者：
Seeburg, PH
中科院分区：
文献类型：
--
作者：
Herb, A;Higuchi, M;Seeburg, PH
通过脑表达的谷氨酸受体（GluR）亚基前mRNA中的腺苷脱氨基作用进行RNA编辑，改变了功能关键位置的基因特异性密码子，例如通道的Q/R位点。我们通过对在PC-12细胞中瞬时表达的小基因的转录分析表明，与GluR-B前mRNA相反，其中两个编辑位点（Q/R和R/G）需要与附近的内含子编辑位点互补序列（ECS）进行碱基配对，GluR 5和GluR 6前mRNA中的编辑招募了位于Q/R位点远端1900个核苷酸的ECS。GluR 5和GluR 6前体mRNA的外显子-内含子双链体结构似乎是双链RNA特异性腺苷脱氨酶的底物。当在HEK 293细胞中共表达时，该酶优先靶向Q/R位点和ECS中未配对位置的腺苷，该位置在脑中被高度编辑。
RNA editing by adenosine deamination in brain-expressed pre-mRNAs for glutamate receptor (GluR) subunits alters gene-specified codons for functionally critical positions, such as the channel's Q/R site. We show by transcript analysis of minigenes transiently expressed in PC-12 cells that, in contrast to GluR-B pre-mRNA, where the two editing sites (Q/R and R/G) require base pairing with nearby Intronic editing site complementary sequences (ECSs), editing in GluR5 and GluR6 pre-mRNAs recruits an ECS located as far as 1900 nucleotides distal to the Q/R site. The exon-intron duplex structure of the GluR5 and GluR6 pre-mRNAs appears to be a substrate of double-stranded RNA-specific adenosine deaminase. This enzyme when coexpressed in HEK 293 cells preferentially targets the adenosine of the Q/R site and of an unpaired position in the ECS which is highly edited in brain.