Regulation of alternative splicing by RNA editing
Regulation of alternative splicing by RNA editing
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DOI：
10.1038/19992
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发表时间：
1999-05-06
期刊：
影响因子：
64.8
通讯作者：
Emeson, RB
中科院分区：
文献类型：
--
作者：
Rueter, SM;Dawson, TR;Emeson, RB
ADAR2酶是一种双链RNA特异性腺苷脱氨酶，通过腺苷到肌苷(1-3)的定点转换参与哺乳动物信使RNA的编辑。在这里，我们识别了几个大鼠ADAR2 mRNAs，它们是由两个不同的选择性剪接事件产生的。一个这样的剪接事件使用了近端的3‘受体位点，在ADAR2编码区增加了47个核苷酸，改变了成熟ADAR2转录本的预测阅读框架。对ADAR2基因组DNA的核苷酸序列分析表明，腺苷-腺苷(AA)和腺苷-鸟苷(AG)二核苷酸分别存在于这些替代3‘受体的近端和远端。近端3‘端受体的使用取决于ADAR2编辑自己的前-mRNA的能力，将内含子AA转化为腺苷-肌苷(Al)二核苷酸，有效地模拟了通常在3’剪接点发现的高度保守的AG序列。我们的观察表明，RNA编辑可以作为一种调节选择性剪接的机制，他们提出了一种新的策略，通过这种策略，ADAR2可以调节自己的表达。
The enzyme ADAR2 is a double-stranded RNA-specific adenosine deaminase which is involved in the editing of mammalian messenger RNAs by the site-specific conversion of adenosine to inosine(1-3) Here we identify several rat ADAR2 mRNAs produced as a result of two distinct alternative splicing events. One such splicing event uses a proximal 3' acceptor site, adding 47 nucleotides to the ADAR2 coding region, changing the predicted reading frame of the mature ADAR2 transcript. Nucleotide-sequence analysis of ADAR2 genomic DNA revealed the presence of adenosine-adenosine (AA) and adenosine-guanosine (AG) dinucleotides at these proximal and distal alternative 3' acceptor sites, respectively. Use of the proximal 3' acceptor depends upon the ability of ADAR2 to edit its own pre-mRNA, converting the intronic AA to an adenosine-inosine (Al) dinucleotide which effectively mimics the highly conserved AG sequence normally found at 3' splice junctions. Our observations indicate that RNA editing can serve as a mechanism for regulating alternative splicing and they suggest a novel strategy by which ADAR2 can modulate its own expression.