Nascent-seq indicates widespread cotranscriptional RNA editing in Drosophila.
Nascent-seq indicates widespread cotranscriptional RNA editing in Drosophila.
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DOI：
10.1016/j.molcel.2012.05.002
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发表时间：
2012-07-13
期刊：
影响因子：
16
通讯作者：
Rosbash, Michael
中科院分区：
文献类型：
--
作者：
Rodriguez, Joseph;Menet, Jerome S.;Rosbash, Michael
RNA编辑酶ADAR将腺苷(A)化学修饰为肌苷(I)，而肌苷被核糖体解释为鸟苷。在这里，我们通过从成年果蝇头部分离新生RNA并对样品进行高通量测序来评估果蝇的A-to-I共转录编辑。在新生的外显子中有大量的编辑位点。来自ADAR零突变株的新生RNA也被测序，表明几乎所有的A-to-I事件都需要ADAR。此外，mRNA编辑水平与同源新生RNA序列中的编辑水平相关，表明编辑程度是共转录设置的。令人惊讶的是，这些新生的数据还发现了内含子编辑位点多于外显子编辑位点。这些内含子位点优先出现在共转录剪接不良的内含子中，表明编辑和剪接之间存在联系。我们得出结论，adar介导的编辑比以前指出的更广泛，并且主要发生共转录。
The RNA editing enzyme ADAR chemically modifies adenosine (A) to inosine (I), which is interpreted by the ribosome as a guanosine. Here we assess cotranscriptional A-to-I editing in Drosophila, by isolating nascent RNA from adult fly heads and subjecting samples to high throughput sequencing. There are a large number of edited sites within nascent exons. Nascent RNA from an ADAR null mutant strain was also sequenced, indicating that almost all A-to-I events require ADAR. Moreover, mRNA editing levels correlate with editing levels within the cognate nascent RNA sequence, indicating that the extent of editing is set cotranscriptionally. Surprisingly, the nascent data also identify an excess of intronic over exonic editing sites. These intronic sites occur preferentially within introns that are poorly spliced cotranscriptionally, suggesting a link between editing and splicing. We conclude that ADAR-mediated editing is more widespread than previously indicated and largely occurs cotranscriptionally.
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