A novel tissue-specific alternatively spliced form of the A-to-I RNA editing enzyme ADAR2.

A novel tissue-specific alternatively spliced form of the A-to-I RNA editing enzyme ADAR2.
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DOI:
10.4161/rna.7.2.11568
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发表时间:
2010-03
期刊:
影响因子:
4.1
通讯作者:
Sperling R
Sperling R
中科院分区:
生物学3区
文献类型:
--
作者:
Agranat L;Sperling J;Sperling R

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ADAR 2是腺苷脱氨酶蛋白质家族的成员,是编辑GluR-B转录物中Q/R位点的酶,这是一种重要的生理A至I编辑事件。ADAR 2前mRNA经历许多已知的选择性剪接事件,影响其功能。在这里,我们描述了一种新的选择性剪接外显子,位于人类基因的内含子7内,我们称之为“外显子7a”。该可变剪接外显子在哺乳动物ADAR 2基因中高度保守。它在所有三个框架中都有终止密码子,并被NMD下调。我们发现,外显子7a的包容性水平在不同的人体组织之间存在差异,骨骼肌,心脏和睾丸中的包容性水平最高。在已知编辑水平高的大脑中,外显子7a包含的水平低。新的替代形式也在构成核前mRNA加工机器的超剪接体中发现。新型ADAR 2选择性外显子在哺乳动物中的高度保守性表明该外显子的生理重要性。
ADAR2, a member of the adenosine deaminase family of proteins, is the enzyme that edits the Q/R site in the GluR-B transcript, an important physiological A-to-I editing event. ADAR2 pre-mRNA undergoes a number of known alternative splicing events, affecting its function. Here we describe a novel alternatively spliced exon, located within intron 7 of the human gene, which we term “exon 7a”. This alternatively spliced exon is highly conserved in the mammalian ADAR2 gene. It has stop codons in all three frames and is down regulated by NMD. We show that the level of exon 7a inclusion differs between different human tissues, with the highest levels of inclusion in skeletal muscle, heart and testis. In the brain, where the level of editing is known to be high, the level of exon 7a inclusion is low. The new alternative form was also found in supraspliceosomes, which constitute the nuclear pre-mRNA processing machine. The high conservation of the novel ADAR2 alternative exon in mammals indicates a physiological importance for this exon.
DOI: 10.1038/emboj.2009.244
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