Novel exon of mammalian ADAR2 extends open reading frame.
Novel exon of mammalian ADAR2 extends open reading frame.
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DOI：
10.1371/journal.pone.0004225
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Gommans, Willemijn M.
中科院分区：
文献类型：
--
作者：
Maas, Stefan;Gommans, Willemijn M.
通过RNA编辑的前mRNA的转录后加工显著地有助于哺乳动物转录组的复杂性。通过位点选择性A-to-I修饰的RNA编辑也通过基因组特定序列的重新编码来调节蛋白质功能。腺苷脱氨酶ADAR 2是负责重新编码编辑的主要酶，并且小鼠中ADAR 2功能的丧失导致癫痫和过早死亡的表型。虽然已知A到I RNA编辑受到发育和细胞类型特异性调节，但关于体内调节RNA编辑的机制知之甚少。因此，表征阿达尔表达和鉴定替代阿达尔变体是理解RNA编辑调控机制和疾病中失调原因的重要前提。在这里，我们提出了一个新的ADAR 2剪接变异体的证据，通过利用位于先前注释的第一个编码外显子上游18个碱基的外显子，并由候选的替代启动子驱动，将ADAR 2的开放阅读框延长了49个氨基酸。有趣的是，49个氨基酸的延伸包含一个与ADAR 3的R结构域密切相关的序列基序，其中它已被证明作为一个基本的单链RNA结合结构域发挥作用。定量表达分析表明，新的ADAR 2剪接变体的表达是组织特异性的，在小脑中最高。人、小鼠和大鼠ADAR 2基因之间ADAR 2 R结构域的强序列保守性表明这种RNA编辑酶的同种型具有保守的功能。
The post-transcriptional processing of pre-mRNAs by RNA editing contributes significantly to the complexity of the mammalian transcriptome. RNA editing by site-selective A-to-I modification also regulates protein function through recoding of genomically specified sequences. The adenosine deaminase ADAR2 is the main enzyme responsible for recoding editing and loss of ADAR2 function in mice leads to a phenotype of epilepsy and premature death. Although A-to-I RNA editing is known to be subject to developmental and cell-type specific regulation, there is little knowledge regarding the mechanisms that regulate RNA editing in vivo. Therefore, the characterization of ADAR expression and identification of alternative ADAR variants is an important prerequisite for understanding the mechanisms for regulation of RNA editing and the causes for deregulation in disease. Here we present evidence for a new ADAR2 splice variant that extends the open reading frame of ADAR2 by 49 amino acids through the utilization of an exon located 18 kilobases upstream of the previously annotated first coding exon and driven by a candidate alternative promoter. Interestingly, the 49 amino acid extension harbors a sequence motif that is closely related to the R-domain of ADAR3 where it has been shown to function as a basic, single-stranded RNA binding domain. Quantitative expression analysis shows that expression of the novel ADAR2 splice variant is tissue specific being highest in the cerebellum. The strong sequence conservation of the ADAR2 R-domain between human, mouse and rat ADAR2 genes suggests a conserved function for this isoform of the RNA editing enzyme.
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影响因子：
7
作者：
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